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2009 Annual Report - ALZHEIMER'S


									            THE McCUSKER


Alzheimer’s disease is one of the most           Hollywood Private Hospital and Edith Cowan
important public health problems we face.        University whose contributions of laboratory
It has a devastating impact on individuals       space, salaries and funding of research costs
and their families, the community and the        are invaluable.
economy. Unfortunately, compared to many
                                                 Particular thanks go to a number of significant
other major health areas such as heart
                                                 donors. These include Helen Sewell, Warren
disease and cancer, it receives little funding
                                                 Milner, Margaret Feilman, Wesfarmers, AFM
for research to discover treatments.
                                                 Adams Charitable Trust and Jim and Jocelyn
The support given by the public to the fight     Everett, Michael Bussell, Mrs Roma Russell
against Alzheimer’s disease is of the utmost     and Mr Mark Turner.
importance. Without the very generous
                                                 We are grateful to community groups such
contributions of time and money made by
                                                 as Lions clubs WA, Rotary and Freemasons
individuals and corporations, the major
                                                 who support our efforts to find a cure
research being undertaken here in WA at the
                                                 for Alzheimer’s disease. Our developing
McCusker Alzheimer’s Research Foundation
                                                 partnership with the Lions Clubs International
would struggle.
                                                 (WA) is particularly appreciated.
We are very grateful to our many supporters
                                                 Volunteers make an invaluable contribution.
who share our vision of a world where
                                                 Their contributions as research volunteers
Alzheimer’s disease is treatable and
                                                 and assistance in fund raising and promotion
preventable and our belief that the research
                                                 are critical to our efforts. Special thanks
occurring here in WA can make major
                                                 go to the volunteers who ran many events
contributions to defeating Alzheimer’s.
                                                 and to Dean Cox, whose support of the
We are especially thankful to the McCusker       Foundation is greatly appreciated.
family, particularly Malcolm, Carolyn and
                                                 Finally, there are many more important
Tonya for their tremendous support and
                                                 supporters we have not singled out, however
assistance over many years. Special mention
                                                 we wish to acknowledge their generous
must also be made of Trevor and Terri Delroy
                                                 support, along with the support of many
for their magnificent and extremely generous
                                                 members of the public.
support both financially and personally and to
Chairman's Report              2

Research Report                4

Clinical Trials Division       26
Alzhyme Pty Ltd                27

Centre of Excellence in
                                    ANNUAL REPORT 2009

Alzheimer’s Disease Research   28

Board Membership               30

Financial Statements           31

    At the beginning of 2009, as              Our research team continues to          the Hon. Barry House MLC, the Hon
    chairman of the McCusker                  forge ahead on several fronts as        Jim Chown MLC and the former
    Alzheimer’s Research Foundation,          outlined in the research report.        member for Moore, Gary Snook.
    I faced the year with great               The major focus of developing
    apprehension. Several important           an early diagnosis blood test           Our Clinical Trials Division continues
    sources of funding had either been        received a significant boost with       its valuable work in trialling
    reduced or stopped and it seemed          the awarding of a substantial           potential new therapies that may
    almost inevitable that we would           grant from the West Australian          assist people suffering the scourge
    operate a deficit and run down its        Government. During 2010 the             that is Alzheimer’s Disease. A
    reserves. Thankfully due to effort        Government will provide $605,000        significant investment by leading
    and some good fortune this has            for the purchase of a high definition   international drug companies is
    been avoided and a surplus of             mass spectrometer for blood             occurring aimed at developing truly
    $179,000 was achieved.                    analysis and $400,000 for brain         effective therapies. Our Clinical
                                              imaging. A further $400,000             Trials Division needs a ready supply
    The surplus does not include              per annum will be provided in           of volunteers to ensure these
    unrealised gains on our share             the following three years for           treatments can be fully assessed
    market investments that were              brain imaging. The grant totals         as to their effectiveness. Professor
    made to achieve higher dividend           $2,205,000 over 4 years.                Martins is emphatic that the early
    yields than bank interest. Most of                                                application of beneficial drugs
    these investments took place in late      The mass spectrometer will be           is essential to maximise their
    2008 and in early 2009 when share         the property of the Foundation but      effectiveness. Hence developing an
    values were significantly lower than      it will be based at Edith Cowan         early diagnosis blood test is most
    now. I thank the Board for being          University, Joondalup. Any spare        urgent even for existing therapies.
    prepared to support a then difficult      capacity for this equipment can
    decision that looks better now!           be utilised by other research           The Clinical Trials Division is very
                                              disciplines, at their cost. The brain   important to the Foundation with all
    One of the highlights of the year         imaging will be conducted at cost       surplus funds being available for the
2   has been Professor Martins’               by Professor Nat Lenzo who is           research effort. Particular thanks
    achievement of becoming the West          developing a new imaging facility at    go to Dr Roger Clarnette and Ms
    Australian, Australian of the Year,       Hollywood Private Hospital.             Felicite Kelsall for their great efforts
    a recognition well deserved. This                                                 in operating the trials.
    award has enhanced further the            Particular thanks go to the Treasurer
    credibility of his work and will assist   and Minister for Science, the           During 2009 our Foundation
    us as a Foundation in our efforts to      Hon Troy Buswell MLA for his            modified its name to give a greater
    support his research team. Former         understanding and support of this       focus on its role in Alzheimer’s
    Board member John Davies prepared         vital project. We are also grateful     research. The new name, the
    the winning submission and we are         for the fantastic advocacy and          McCusker Alzheimer’s Research
    most grateful for his efforts.            support we received from the            Foundation also provides greater
                                              President of the Legislative Council    distinction from the McCusker
                       Our Foundation benefits greatly from
                       people who give us substantial support.

families own entities such as the       Our Foundation benefits greatly          Dr Judy Edwards has been
McCusker Charitable Trust and           from people who give us substantial      appointed as the new Executive
McCusker Family holdings. The           support. Particular mention must be      Manager and the Board is confident
McCusker Alzheimer’s Research           made of the Delroy, McCusker and         she will prove most valuable to our
Foundation is legally quite separate;   Everett families as well as Warren       future progress.
however, the McCusker family have       Milner, Helen Sewell and Michael
been most generous over the years       Bussell. Wesfarmers and Hollywood        As Chairman I must pay tribute to
in supporting Professor Martin’s        Private Hospital have continued          Professor Martins, our Director
work, starting with the great Sir       their valuable support as has the        of Research and his wonderful
James McCusker through to today         wonderful Margaret Feilman of the        team. Their enthusiastic and good
where Malcolm McCusker AO QC            Feilman Foundation. During the year      natured dedication to our important
is our most valued Patron. Other        Anne and Tony Rawson organised           goal is inspiring to those of us
family members’ support is also         two functions in the Margaret            associated with them. Professor
much appreciated. Accordingly I         River area. One was a successful         Martins’ leadership and the
was delighted to see the McCusker       film night and the other a dinner at     dedicated support provided to him
name retained in our title.             Voyager Estate Winery that raised        by Lieutenants Kevin Taddei and
                                        over $10,000. Thanks go to them          Giuseppe Verdile, Matt Sharman
Further progress will be the            and Voyager Winery. Terrina Brown        and Simon Laws, has achieved
Foundation’s purchase of two            of Zedz Spa du Jour also continued       loyalty and productivity throughout
properties during 2010. One in          her vital support, for which we          the team.
Nedlands is close to our current        are very grateful. The Foundation
rented premises and the other                                                    Finally our Board is functioning
                                        was particularly blessed to receive      well with individual members
is in the new Specialist Medical        $100,000 in a bequest from the
Centre on site at Hollywood Private                                              undertaking special tasks that
                                        estate of Max Shepherd in Victoria.      contribute to our big picture
Hospital. The research activities
will be primarily based at Nedlands     This year will see a complete change     objectives. My special thanks to
with administration based at the        in Foundation administration staff       our dedicated office bearers, the
Hollywood site along with other         with both Tim Doncon and Margaret        Deputy Chairman Dr Terry Bayliss        3
clinical activities. The Foundation     Lewis resigning. I thank them both       and the Treasurer Peter Stevens.
will gain approximately 100 square      for their loyalty and cooperation        Both members have performed
                                                                                 above and beyond the call of duty.
                                                                                                                         ANNUAL REPORT 2009

metres of space and save money          during my time as Chairman and on
in rent.                                behalf of the Board I extend them        I express my gratitude to everyone
                                        every good wish for their futures.       who has contributed to the
The purchases have been made            I believe both will retain a link with
possible thanks to Lotterywest and                                               Foundation in 2009, assisting us to
                                        the Foundation.                          end the year far more successful than
the earlier capital contributions
from the McCusker and Delroy                                                     I believed possible at its beginning.
families. Board member Jenny Day
played a vital role in our success
with Lotterywest.
    Prof Ralph Martins, Director of Research

    The past year has been a                These areas are considered              This world leading research,
    year of great progress in our           of prime importance because             conducted in partnership with
    research and this is entirely due       we believe that, despite many           the CSIRO and collaborators
    to the continuing support and           potential drugs being identified,       from Melbourne University and
    encouragement we receive from           a publicly available treatment is       the Austin hospital, involves
    our many supporters and the public      still some time away, due to the        both the study of beta amyloid
    as well as the magnificent efforts      lengthy processes required to           accumulation in the brain as a
    of our team members. Due to this        prove the safety of any treatment       potential early diagnostic marker
    effort and support our research         prior to public release. On the other   and also the study of the potential
    achieved a number of milestones         hand, lifestyle factors capable of      of lifestyle factors to prevent or
    in 2009.                                deferring or preventing the onset       delay the onset of AD. This is a
                                            of Alzheimer’s are available as         major study that is increasingly
    Basically we undertake Alzheimer’s      soon as their efficacy is proved.       receiving recognition for its
    disease research in four areas:         Equally important is to be able to      considerable potential to identify
    understanding the pathology             provide people with a diagnosis of      lifestyle interventions that could
    of the disease; development of          early onset or of heightened risk,
4                                                                                   defer the onset of Alzheimer’s.
    treatments; identification of factors   so that they can make an informed
    with the potential to defer or          decision as to whether and how to       As part of our research into a
    prevent the onset of the disease;       modify their lifestyle.                 diagnosis, we have established
    and the discovery of tools for an                                               the latest advancement in AD
    early diagnosis.                        In the Australian Imaging, Biomarker    research, PET-PIB, in Perth,
                                            and Lifestyle (AIBL) Flagship Study     allowing detection of the
    Currently we have a major focus on
                                            of Ageing, our research team has        accumulation of beta amyloid in
    the discovery of an early diagnosis
                                            completed baseline screening for        the living brain. This is a first in
    and the identification of factors
                                            1112 participants.                      Western Australia and allows us to
    that can defer or prevent the onset                                             study the link between the level of
    of Alzheimer’s.                                                                 beta amyloid accumulation and risk
                                                                                    of Alzheimer’s.
                       Exciting breaking news is the recent announcement
                       by the West Australian State Government of a grant
                       of $2,205,000.00 over four years for the discovery of
                       biomarkers for the early diagnosis of Alzheimer’s disease.

Our research has now established        We also received funding for           We continue to progress potential
that beta amyloid is a diagnostic       research into a major study            therapeutic strategies, particularly
marker, but it is not sufficiently      into the preventative value of         beta amyloid neutralising agents
reliable on its own. In collaboration   specific nutritional supplements       and testosterone. We have now
with our AIBL partners and with         for AD. This study will focus on       been able to provide dedicated
researchers in Singapore and the        the potential of antioxidants and      staff to some projects and as a
USA, we are developing ways to          poly phenols to defer the onset of     result we anticipate accelerated
identify a suite of bio-markers         Alzheimer’s and is a major aspect      progress in these studies.
which, when used together,              of our program to identify lifestyle
will provide an accurate and            factors that can reduce or defer       Exciting breaking news is the
reliable diagnostic test for AD.        the onset of Alzheimer’s. Animal       recent announcement by the West
We remain highly optimistic of          experiments are currently underway     Australian State Government of
achieving this important objective                                             a grant of $2,205,000.00 over
                                        to determine what antioxidant
provided adequate funding is                                                   four years for the discovery of
                                        combination, and in what amounts,
made available. In the last 12                                                 biomarkers for the early diagnosis
                                        will reduce or even block the
months, using the latter approach,                                             of Alzheimer’s disease.
                                        accumulation of beta amyloid in the                                           5
we have already identified a            brains of these animals.               The following is an overview of the
panel of biomarkers that together                                              major research projects and related
                                                                                                                      ANNUAL REPORT 2009
                                                                                                                      ANNUAL REPORT 2009

with our recent findings of blood                                              activities the Sir James McCusker
apolipoprotein E (apoE) levels                                                 Alzheimer’s Disease Research
being altered in AD has greatly                                                Laboratory is undertaking.
increased the diagnostic accuracy
previously achieved, but other key
biomarkers need to be identified
for this panel to be completed.

               The Dominantly Inherited Alzheimer’s Network (DIAN) study

               The McCusker Alzheimer’s Research Foundation and           gained from DIAN may lead to tests that detect
Kevin Taddei   Edith Cowan University are one of the sites for the        people who still are normal but are at very high
               Dominantly Inherited Alzheimer’s Network (DIAN)            risk of developing dementia caused by AD. All
               study. This US$16 million international Network has        DIAN participants will be members of families with
               been established by the National Institute on Aging of     dominantly inherited AD caused by a known mutation
               the National Institutes of Health (US) to bring together   and may be ideal candidates to participate in future
               researchers who study genetic forms of Alzheimer’s         studies of drugs that have the potential to halt the AD
               disease (AD). The study is seeking 400 volunteers who      process and prevent dementia.
               are members of families in which AD is dominantly
               inherited, meaning that about 50% of the individuals       Presently, there are 10 DIAN study sites: six in the
               in each generation of a family develop AD, generally       US, one in England, and three in Australia. Research
               before age 60. These rare forms of AD are caused by        volunteers travel to one of the sites for the studies,
               a mutation in one of 3 known genes. Each child of an       which are repeated every few years. It is expected
               affected parent has a 50% chance of inheriting the         that each round of DIAN studies will take between 3
               mutation. If they do, they will develop the dementia       and 5 days to complete. Participants may benefit from
               of AD at about the same age as their parent. Siblings      the opportunity to talk with persons knowledgeable on
               who do not have the mutation have no greater risk          the autosomal dominant form of Alzheimer’s disease.
               of developing AD than someone without a family             The Australian sites include the McCusker Alzheimer’s
               history of AD and will participate in DIAN as part of a    Research Foundation, Edith Cowan University, Prince
               comparison group for their mutation-carrying siblings.     of Wales Medical Research Institute, University of
               Individuals participating in DIAN are not required to      New South Wales, Mental Health Research Institute
               know whether or not they carry a mutation. Should          of Victoria and the University of Melbourne.
               they wish to learn their mutation status through
               genetic testing following genetic counseling, DIAN         Further information about DIAN can be found at:
    6          can assist with this process.                     or please contact

               Research suggests that brain changes may occur             Athena Paton at the McCusker Alzheimer’s Research
               years before actual Alzheimer’s symptoms are               Foundation on (08) 9347 4200, by fax 08 9347 4299,
               detected. The major goal of DIAN is to study these         mobile 0418 939 233
               changes in people who carry an AD mutation to              or email:
               determine how the disease process develops before
               there are any symptoms. Ultimately, knowledge
Hearts and Minds: the link between cholesterol and brain health.
McCusker Alzheimer Research Unit : Memory Complainer Study

It’s often said, “what’s good for the heart is good for   In this study, we show that higher levels of HDL are
the mind”, but now, data from one of the research         associated with lower levels of Aß. Higher levels          Dr Kristyn Bates
studies conducted at The McCusker Foundation              of HDL are in turn linked with good cardiovascular
supports this adage.                                      health and reduced risk of heart disease and stroke.
                                                          This finding provides a possible mechanism linking
The project is called “Molecular and                      cardiovascular disease to AD and if proven causal,
Neuropsychological Predictive Markers of Cognitive        may lead to the development of new preventative
Decline” and is a multidisciplinary approach to           strategies. In particular, lifestyle changes that
enhance the diagnosis of Alzheimer’s disease (AD).        promote physical activity and fitness, which boost
One of the biggest issues for the development of          HDL levels, may reduce Aß and protect the brain
policies for aged health care is that there is not a      against AD.
predictive test for AD, which is the major cause
of dementia. The main aim of this project is to           We are currently preparing more data for publication
investigate the association between biochemical,          this year. These results describe the effects of genetic
brain imaging and neuropsychological factors that         risk factors on cognition and neuronal activity, the
may predict cognitive decline and the development         relationship between HDL and improved learning and
of AD. By developing accurate, early diagnostic           memory performance and a characterisation of the
strategies, appropriate therapeutic or preventative       memory complaints reported by study participants.
interventions for AD can be implemented prior to
                                                          In 2009, we embarked on a lifestyle intervention trial
disease onset.
                                                          on memory study participants to assess the benefits of
The study recruits individuals with or without            cognitive and physical activity on memory performance.
subjective memory complaints (SMC). A variety of
                                                          These projects are crucial as they lead to the
neuropsychological, clinical and biochemical analyses
                                                          development of early diagnostic tests that in turn will
are performed to generate a “high risk” profile.
                                                          result in more effective preventive and therapeutic
Positron emission tomography (PET) is also being                                                                             7
                                                          approaches. We are now moving from purely
used to image the brain and identify hallmarks of the
                                                          observational studies, to those testing intervention
disease (i.e. beta amyloid deposition). These brain
                                                          strategies. In other words, translating research into
                                                                                                                             ANNUAL REPORT 2009
                                                                                                                             ANNUAL REPORT 2009

imaging studies are being conducted in collaboration
                                                          practice and this is an exciting progression for our
with the Austin Hospital and will assess the possible
                                                          research team.
predictive value of PET imaging for AD.
                                                          This important transition could only have been made
Using data from this study, we have uncovered a
                                                          possible through the continued support from our study
relationship between the level of HDL, or “good
                                                          participants who so generously volunteer their time
cholesterol” and Aß in the blood (Journal of
                                                          to our studies. We thank them for participating in our
Alzheimer’s Disease 17: 305-318, 2009).
                                                          research projects.

                  Olfactory Dysfunction: A potential screening approach for Alzheimer’s disease?
                  McCusker Alzheimer Research Unit : Memory Complainer Study

                  Alzheimer’s disease (AD) is the most common               On the other hand, there are three different findings
Hamid R Sohrabi   cause of dementia. However, the diagnosis of AD is        indicating an association between the olfactory
                  usually possible only late in the process of disease      system and the diagnosis of the AD. It has been
                  progression. By the time AD can be diagnosed, based       shown that a significant loss of the sense of smell
                  on current medical interventions, the brain cells have    is associated with dementia, and in addition, that
                  been irreversibly affected. Therefore the best option     olfactory problems have been reported in:
                  is to screen and detect individuals at higher risk for    i) AD patients;
                  developing the disease and so start prevention and        ii) people at genetic risk for AD; and in
                  intervention at a very early stage or even prior to any   iii) patients with mild cognitive impairment (MCI) - a
                  brain pathology. Currently, different AD screening        proposed precursor to AD. Therefore, we tried to see
                  methods are under investigation. One of these             if the olfactory function can differentiate between
                  methods is the assessment of olfactory functions.         those individuals who have some serious complaints
                                                                            about their everyday memory performance and those
                  In the brain, two regions are highly involved in the
                                                                            who did not present with such complaints. In some
                  memory functions, namely the hippocampus and
                                                                            studies, it has been shown that those with serious
                  entorhinal cortex. These two brain regions are the
                                                                            complaints about their memory functions are at higher
                  very primary sites affected by AD neuropathological
                                                                            risk of developing AD.
                  processes. In addition, they are the main brain regions
                  with close connections to the olfactory system. In        In the first round of our study, we found that there
                  fact, the olfactory system is the only sensory organ      is a significant relationship between complaints
                  that has direct projections to the above mentioned        about memory and the decline in the performance
                  memory regions of the brain (See Figure1).                of olfactory sense. In addition, we showed that the
                                                                            greater the frequency and severity of the complaints,
                                                                            the more loss of olfactory functions. The next step
                                                                            would be to find the relationship between losing the
                                                                            sense of smell and cognitive decline in this group of
                                                                            participants. We also need to find if the olfactory
                                                                            functions decline more amongst those individuals who
                                                                            are carrying specific genetic risk factors for AD. Also,
                                                                            the association of olfactory decline with increasing
                                                                            AD-related neuropathology in the brain that can be
                                                                            visualized through brain scans with positron emission
                                                                            tomography (PET) could be of significant importance
                                                                            in showing the actual value of this non-invasive
                                                                            assessment method.

                  Figure 1
Research into Amyloid Beta as a potential biomarker for use in diagnosis of Alzheimer’s
disease in blood (AIBL study)

With research in preventative medicine and early            techniques to explore the usefulness of plasma Aß as
treatment gaining fast momentum in Alzheimer’s              a diagnostic tool for AD.                                  Dr James Lui
disease (AD), the importance of diagnosis,
in particular early diagnosis will play an integral part    We conducted a large study using a cohort of over
in improving the quality of life of prospective sufferers   1100 participants that was recruited across two cities
through early treatment and life style changes.             (Perth and Melbourne) with a standard set of criteria
Successful diagnostics for AD will depend on valid          according to Ellis et al, 2009. Standard batteries of
biomarkers with which we may gauge                          neuropsychological assessments were conducted
pre-symptomatic changes of the disease.                     in order to class participants into three categories
                                                            – human control participants (HC), mild cognitive
On top of the growing list of possible biomarkers of        impaired patients (MCI) and Alzheimer’s disease
AD is Amyloid-ß (Aß), the main component of amyloid         patients (AD). Blood plasma samples were analysed
plaques. Clinical neuropsychological assessments            for the levels of the two isoforms Aß 1-40 and Aß 1-42
and post-mortem examinations have established               using the INNO-BIA Aß detection kits (Innogenetics
that the formation of amyloid plaques is a major            Inc.), as well as an established double sandwich ELISA
symptom of AD. However, the measurement of Aß               assay (Mehta).
and its significance in relation to AD is still unclear.
The intimate relationship of Aß in the pathology of AD      We found that Aß 1-42 had a decreasing trend in AD
has prompted many in the past to characterise and           participants when compared with HC participants.
assess its usefulness as a biomarker. Detection of          This also resulted in a decreasing trend for the Aß1-42/
two major variants of Aß in cerebrospinal fluid (CSF)       Aß1-40 ratio from HC to AD participants. Given that
has been well established. However, the high degree         Aß is 100 fold lower in blood plasma than in CSF and
of invasiveness involved in CSF collection prevents its     that there are many interfering proteins which may be
usefulness for detection in the wider community. A          interacting with and/or degrading Aß in plasma,
more accepted approach is analysis through collected        it is perhaps not surprising to see that although there
blood products. This attractive alternative utilises        is an existing trend, the results were only marginally           9

existing facilities that are more accessible in the         statistically significant.
community and translates to better accessibility and        Another concern raised through this study so far, is
                                                                                                                             ANNUAL REPORT 2009
                                                                                                                             ANNUAL REPORT 2009

lower cost. Unfortunately, available studies to date        that values of Plasma Aß measurements could differ
utilising blood plasma have shown conflicting results.      between different assaying methods, although the
A combination of technical inconsistencies, such as         general trend remained the same. This may explain
low numbers of participants in these studies, together      the reason for such large discrepancy between
with differences in technical procedures, could be the      previous studies. The comparison of this study
contributing factors to variations in the end results.      indicates that different antibodies used for the assay
Our interest is to address these inconsistencies and        as well as technical differences in the assaying
develop new techniques, as well as optimizing current       method itself, will lead to incomparable results.

     One of the ongoing aims of our group will be to tease   1. Ellis K A, Bush A I, Darby D, De Fazio D, Foster J,
     out the differences through deeper understanding of        Hudson P, Lautenschlager N T, Lenzo N, Martins
     the mechanism of these assays.                             R N, Maruff P, Masters C, Milner A, Pike K, Rowe
                                                                C, Savage G, Szoeke C, Taddei K, Villemagne V,
     In contrast to previous studies, our use of a large        Woodward M, Ames D, and null, t. A. R. G. (2009)
     cohort ensures higher statistical confidence of our        The Australian Imaging, Biomarkers and Lifestyle
     results. The findings of this study so far indicate        (AIBL) study of aging: methodology and baseline
                                                                characteristics of 1112 individuals recruited for
     that cross sectional studies of blood plasma Aß
                                                                a longitudinal study of Alzheimer’s disease,
     measurements alone cannot determine differences            International Psychogeriatrics 21, 672-687.
     between AD patients and HC, although extension
                                                             2. Lui J, Laws S M, Li Q-X, Villemage V L, Ames D,
     to longitudinal studies of blood plasma Aß                 Brown B, Bush A I, De Ruyck K, Dromey J, Ellis K
     measurements may determine greater differences             A, Faux N G, Foster J, Fowler C, Gupta V, Hudson
     between AD patients and HC. In addition, plasma            P, Laughton K, Masters C L, Pertile K, Rembach
     Aß measurement on its own may not be of value in           A, Rimajova M, Rodrigus M, Rowe C C, Rumble R,
     determining the difference between an AD patient           Szoeke C, Taddei K, Taddei T, Trounson B, Ward
     and a normal individual. However, Aß in combination        V, Martins R N and, AIBL Research Group (2010)
     with a panel of other markers of AD may still be           Plasma amyloid-ß as a biomarker in Alzheimer’s
                                                                disease: the AIBL study of ageing, Journal of
     useful as a quick and simple community wide test in
                                                                Alzheimer’s Disease (accepted 19 Feb 2010,
     determining the difference between AD patients and         #10-249)
     normal individuals.

     With the second phase of the AIBL study on the way,
     incorporating data collected at 18 months from the
     time of the phase I studies, these hypotheses will be
     tested and a clearer relationship between Aß and AD
10   may emerge. A paper manuscript entailing the AIBL
     Phase I study contains further details of results and
     explanation of this study.
ApoE as a blood biomarker (AIBL study)

Project Aims: This project will contribute to the          Major Findings to date: Our preliminary data (Gupta
overall aim of identifying biomarkers (substances used     et al, manuscript submitted), from AIBL (Australian
as an indicator of a biological state), which will allow   Imaging Biomarkers and Lifestyle) cohort, shows a
for the development of a sensitive and specific means      decline in plasma ApoE levels in AD corresponding
for an early diagnosis of Alzheimer’s disease (AD).        with a significant negative correlation with brain
Apolipoprotein E (apoE) is one such protein associated     amyloid load. The frequency of individuals with apoE4
with lipoproteins and is involved in the transport of      isoform was also found to be more in the AD category
lipids in various tissues in the body.                     in the cohort. Overall, individuals with apoE4 isoform
There are different forms of apoE, which differ in their   had significantly lower apoE levels compared to the
lipid association properties as well as conformation       non-apoE4 ones. ApoE levels were also influenced by
and stability. A genetic association between               the ages of the individuals with highest apoE levels in
inheritance of one of the forms of apoE, namely apoE4      the youngest age group of the cohort. The results of
and AD has long been shown but the mechanism               my study at this stage suggest a relationship between
behind this association is still not completely            plasma apoE levels and the risk of onset of AD and
understood. However, it is known to contribute to          also that the presence of apoE4 isoform is associated
AD pathogenesis by directly regulating brain lipid         with lower plasma apoE levels. However, it is unlikely
metabolism and synaptic functions through apoE             to be diagnostically sufficient as an independent
receptors and also by modulating the metabolism and        biomarker because it lacks the required sensitivity and
aggregation of amyloid beta (Aß) peptide.                  specificity for a potential blood biomarker.
Thus the aims of my project are to                         Several other candidate biomarkers for AD such as
i) investigate total apoE and apoE4 specific levels in     Aß and Tau have been identified to date but no single
AD, to                                                     marker could serve all the utilities of a biomarker.
ii) determine its usefulness as a biomarker for AD.        Hence, the diagnostic significance of their contribution
                                                           to a panel of biomarkers remains to be determined
Significance of the project: Current means for the
                                                           and will be assessed in my future work.                    11
definitive diagnosis of AD is dependent upon post-
mortem examination of the brain for evidence of            Future Directions: My future work involves the
the disease’s characteristic neuropathology, namely        development of a Luminex xMAP (multi-analyte
                                                                                                                      ANNUAL REPORT 2009
                                                                                                                      ANNUAL REPORT 2009

extracellular and intracellular amyloid deposits.          profiling) bioassay technology for the estimation of
With advances in research into interventions for AD,       apoE levels in plasma. xMAP technology involves the
in terms of both medical treatments and lifestyle          use of 100 distinct sets of colour-coded beads, called
changes, the development of a reliable method of risk      micro-spheres. Each bead set can be coated with a
stratification is needed.                                  specific antibody allowing the capture and detection
                                                           of a specific analyte from a sample.

                                                           Dr Veer Gupta

                                                                                          Dr. Simon M. Laws
                                                                                          (AIBL study)

     In this way, xMAP technology allows the theoretical       Biomarker discovery and the identification
     multiplexing of up to 100 unique assays within a single   of a diagnostic signature
     sample, both rapidly and precisely. Once the technique
     is successful for the detection of apoE, it will be       Project Aims: Use discovery approaches to identify
     useful for simultaneous detection of other selected       biomarkers (substances used as an indicator of a
     biomarkers such as Aß (work of Dr. James Lui),            biological state), such as proteins in plasma, whose
     Insulin degrading enzyme (work of Ms Michelle Tegg)       measurable levels are altered between healthy and
     and many others from literature and our research,         AD individuals. This will contribute to the overall aim
     including those identified through biomarker screening    of identifying the best set of biomarkers leading to
     (Dr. Simon Laws). This knowledge will be combined to      the development of a means for the early diagnosis of
     create the optimal multiplex diagnostic assay, which      Alzheimer’s disease.
     allows quantification of more than one biomarker
     simultaneously. The multiplex assay technique will        Significance of the project: With advances in
     save both time and the amount of sample, required.        medical treatments and lifestyle interventions for AD,
     In collaboration with the AIBL research team, Dr.         the discovery of biomarkers for the development of a
     Simon Laws, Dr. James Lui and Michelle Tegg (ECU).        reliable method of early diagnosis is paramount. The
                                                               identification of such biomarkers will allow for current
                                                               and future prevention and treatment strategies to be
                                                               initiated when they are most effective and will also
                                                               have applications in the monitoring of medical and
                                                               lifestyle interventions.

                                                               Major Findings to date: As part of the AIBL study,
                                                               biomarker discovery has been undertaken on samples
                                                               collected from volunteers at their initial visits (termed
                                                               baseline). This work was completed in collaboration
                                                               with Rules Based Medicine (RBM, Austin, Texas)
                                                               and used a modified version of their DiscoveryMAP
                                                               quantitative immunoassay service, which allowed
                                                               us to analyse 152 potential biomarkers in blood. This
                                                               enormous amount of data was analysed with the
                                                               assistance of Assoc. Prof. Peng Lam (ECU) and Alinda
                                                               Mondal. Initial data preparation (quality control)
reduced the 152 variables to be analysed to 112, plus       most sensitive and specific panel of biomarkers,
APOE genotype and age. From these 112 variables we          which have the potential to diagnose AD at an early
were able to pin-point a biomarker ‘signature’ of 10        stage. As such we have recently submitted a NHMRC
variables, which after further analysis was reduced         grant that will hopefully provide funding to allow us to
to a 6-marker signature consisting of 4 novel proteins,     take this work to the next level.
APOE genotype (the major genetic risk factor for
                                                            In collaboration with the AIBL research team,
sporadic AD) and age (a major factor for AD risk).
                                                            Assoc. Prof. Marcus Wenk (National University of
The reduced signature provided comparable levels of
                                                            Singapore), Assoc. Prof. Lam, Dr Veer Gupta,
sensitivity (the ability to correctly identify positives
                                                            Dr James Lui, Alinda Mondal (ECU), Dr. Julian
e.g. AD sufferers) and specificity (the ability to
                                                            Rodrigues and Prof. Frank Mastaglia (Australian
correctly identify negatives e.g. non-AD) to the initial
                                                            Neuromuscular Research Institute), Prof. Ian James
10-marker signature. The addition of plasma apoE (the
                                                            (Murdoch University)
work of Dr. Gupta) to the 6-marker signature resulted
in a slight increase in both sensitivity and specificity,   Further, the strong collaborations resulting from the
thus suggesting that plasma apoE is a viable                AIBL study will allow us to thoroughly investigate a
candidate biomarker when included in a biomarker            further ‘-omic’ approach to help identify additional
panel. This work is to be presented at the upcoming         biomarker candidates, as well as increasing our
International Conference on Alzheimer’s Disease             understanding of the pathways leading to the
(ICAD) in Hawaii.                                           development of AD and the identification of
                                                            candidates for drug targeting. This approach will
In collaboration with the AIBL research team,
                                                            focus on the identification of genes, hence termed
Assoc. Prof. Lam, Alinda Mondal, Dr Veer Gupta and
                                                            ‘genomics’. These genomic approaches will aim
Dr James Lui (ECU).
                                                            to identify new genes involved in early onset and
Future Directions: Our recent proteomic (large scale        sporadic AD as well as the screening of genes in
analysis of proteins) findings, including the RBM           the Australian population. This work will initially        13
screening and the plasma apoE and Aß work of Drs            be undertaken with industry collaboration with
Gupta and Lui, respectively, have been promising.           the ultimate goal of bringing a genomics platform
                                                                                                                       ANNUAL REPORT 2009
                                                                                                                       ANNUAL REPORT 2009

This is also the case with the lipidomic (large scale       to ECU in the near future – achieving this goal will
analysis of lipids) work of Ms Florence Lim. Whilst         significantly reduce costs and greatly facilitate our
these independent approaches are both yielding              ability to identify new targets for AD research.
promising candidates the discovery of the optimal
                                                            In collaboration with the AIBL research team,
panel of biomarkers is likely to require a combined
                                                            Sequenom Inc. and GeneWorks Australia
‘multi-omic’ approach. We firmly believe that this
approach stands the best chance of capturing the
                                  PREvENTiON ANd TREATmENT

        Dr Giuseppe Verdile

     Developing agents that selectively target                    thesis for examination in March 2010. His work was
     the enzyme responsible for beta amyloid                      included as preliminary data in a recently submitted
     generation                                                   NHMRC grant. This data will increase our chances of
                                                                  obtaining the grant.
     Background                                                   We continue to collaborate with Dr Imre to purify the
                                                                  enzyme and determine its structure. The next aim will
     The enzyme, gamma secretase is a major target for
                                                                  be to identify areas within the enzyme that are critical
     developing appropriate specific therapeutic agents for
                                                                  for its activity to generate beta amyloid, in the hope of
     Alzheimer’s disease. The enzyme is responsible for
                                                                  developing specific drugs targeting beta amyloid.
     the production of a protein called beta amyloid, which
     has a central role in Alzheimer’s disease pathogenesis.      As well as using this model to determine the structure
     The majority of drugs that have been developed               of the enzyme, we also aim to develop it as a rapid
     targeting the enzyme have failed due to its many             screening method of drugs aimed at reducing beta
     other functions within cells. A better understanding of      amyloid production. Another feature of the enzyme is
     gamma-secretase function and structure is required if        that it also acts on other proteins that are important
     it is to be pursued as an appropriate target. Using the      in cell function. Its multi-functional nature is a major
     latest advanced techniques, the project will provide         reason for the failure of the majority of drugs that have
     significant insight into the function and structure of the   been developed targeting the enzyme. These drugs
     enzyme, and thus can be used to develop more specific        have shown severe side-effects in pre-clinical trials.
     drugs directed at gamma secretase.                           By comparing the effect of potential therapeutic
                                                                  agents on enzyme activity on a number of proteins that
                                                                  are acted on by the enzyme, we can rapidly identify
     The initial stage of this project involves re-constructing   those that specifically target beta amyloid without
     the enzyme in an insect cell culture model. We use this      altering the production the other proteins.
     model to generate large amounts of the enzyme so             This will ultimately generate more specific drugs for
     that it can be purified and undergo structural analysis      the disease.
     to determine its structure, which currently remains
                                                                  Sudarsan and Dr Verdile, together with A/Professor
     to be determined. A PhD student, Mr Sudarsan
                                                                  David Groth and Professor Martins wrote an article on
14   Krishnaswamy was recruited to undertake this project
                                                                  the gamma secretase enzyme that was published in
     in 2007. Initial attempts at re-constructing the enzyme
                                                                  2009 in Critical Reviews in Clinical Laboratory Sciences.
     failed however, after many subsequent attempts we
                                                                  The article received excellent peer reviews including
     finally succeeded at re-constructing all 4 components
                                                                  'This is an outstanding review' and "this is one of the
     that make up the enzyme. This success was possible
                                                                  best organized and most thorough reviews of this topic
     through our collaborations with Dr Imre Berger from
                                                                  that I have ever encountered. I would recommend
     the European Molecular Biology Laboratories (EMBL),
                                                                  publication as is".
     Grenoble, France who is an expert at reconstructing
     complex proteins and indentifying their structure.           This work on re-constructing the gamma secretase
     Sudarsan spent 3 months in his laboratory where he           complex in insect cells will be presented at the
     learnt advanced molecular biological techniques that         International Conference on Alzheimer’s Disease
     he brought back with him. Sudarsan submitted his             (ICAD) July , 2010.
     Belinda Brown                                                                        Dr Tejal Shah and Ellen Putland

The Effect of Physical Activity on Cognition, the                                PEACS Study - Effects of Physical
Development of Alzheimer’s disease and Associated Blood                          Activity and Cognitive Stimulation on
Biomarkers (AIBL study)                                                          Plasma Beta Amyloid and on Cognitive
                                                                                 Functioning in the Elderly
The objective of my research is to determine the effect of physical activity
on the development of Alzheimer’s disease (AD). Four years ago the ABS           Lifestyle modifications as possible preventive
released data from the 2004-05 National Health Survey, which stated              strategies in Alzheimer’s disease (AD) research
that seventy per cent of individuals over the age of 55 reported being           have become an international priority.
sedentary, or undertaking low levels of physical activity. Based on previous     Participation in lifestyle-related behaviors like
statistics of mortality and morbidity, this report estimated that the national   physical and mental activity has been shown
annual cost of physical inactivity was approximately A$377 million. This         to reduce the risk of dementia and AD in
data is of great concern, particularly as physical activity has shown to have    numerous studies. However to be considered
protective properties against AD and other forms of dementia.                    as part of a public health prevention strategy,
                                                                                 more data is required as to the most effective
Data used in my research has been collected from the Australian Imaging
                                                                                 form and delivery of such interventions, and
Biomarkers and Lifestyle (AIBL) Study cohort, which is comprised of 1112
                                                                                 the biological mechanisms that mediate this
individuals. As a part of the AIBL study, participants completed a baseline
                                                                                 protective effect. Animal studies have shown
and 18 month follow-up assessments. These included blood collection
                                                                                 that physical activity clears beta amyloid (Aß)
(for analysis of blood biomarkers), memory testing, and the completion
                                                                                 load thought to be neurotoxic in AD pathology
of a physical activity questionnaire. As well as this, 250 participants
                                                                                 and is also responsible for regeneration of brain
were randomly selected to wear activity monitors. To date, I have had
                                                                                 cells. This concept is yet to be demonstrated in
some interesting results from my research. Firstly, data from the baseline
                                                                                 humans. Additionally, staying mentally active
assessments indicate that higher reported physical activity levels are
                                                                                 increases an individual’s cognitive reserve
associated with decreased blood levels of Amyloid-ß (a toxic protein
                                                                                 capacity and this may help compensate with
associated with AD pathology). In addition to this, physical activity has
                                                                                 the pathological outcomes of AD.
been associated with lower cardiovascular risk factors (which are also
                                                                                 This is validated by an enhancement in speed
risk factors for AD), such as triglycerides, insulin and glucose. Preliminary
                                                                                 of processing, reasoning and memory by mental
analysis of the data collected from the activity monitors shows that higher
                                                                                 stimulation via brain training.
levels of recorded exercise is related to better performance on memory                                                               15
and cognitive tests.                                                             PROJECT SIGNIFICANCE
                                                                                 It is expected that the combination of physical
For the remainder of my PhD I aim to further investigate the mechanism by
                                                                                                                                     ANNUAL REPORT 2009

                                                                                 activity and cognitive stimulation will enhance
which physical activity protects against AD. This will be done by examining
                                                                                 cognitive functioning over that observed
the role physical activity plays in the mediation of numerous AD related
                                                                                 when these interventions are administered
biomarker processes. Results from the 36-month follow-up will also be
                                                                                 separately. The PEACS study is the first project
used to perform an AD risk analysis, i.e. if somebody reports low physical
                                                                                 of its type specially designed to address the
activity levels at baseline, do they have a higher chance of developing
                                                                                 lacuna left behind by previous studies and
AD over 3 years, than somebody that is very physically active? I hope
                                                                                 to establish the clinical significance of the
that these results contribute towards creating a clearer picture as to how
                                                                                 project’s lifestyle intervention program.
physical activity may contribute to long lasting cognitive health.
     Further, for the first time, the effects of physical      and 52 weeks). The assessment criteria include
     activity and cognitive stimulation will be assessed       neuropsychological and clinical tests, measurement of
     on blood and cerebrospinal fluid (CSF) biomarkers         AD-related blood and cerebrospinal fluid biomarkers,
     and will be correlated with cognitive functioning and     brain scans (FDG PET) and DXA scans (for body fat
     thus provide insight into the potential mechanisms        and body composition).
     by which these interventions improve memory and
                                                               Current Status of the Project
     learning. Further, the effects of the interventions
     on brain glucose utilisation assessed by FDG-PET          The project is currently ongoing. Phase 1 was
     scanning will provide further insight into how physical   completed (56 participants) in December 2009.
     activity and cognitive stimulation interventions          Phase 2 is currently ongoing (68 participants).
     improve neuronal metabolism which contributes to          Phase 3 will commence from June 2010. Interested
     improved neurotransmission and cognitive functioning.     participants can please contact Ellen or Tejal on 9347
     Should the intervention(s) prove successful, this study   4206 for further information.
     would be expanded to assess multiple strategies with
     the ultimate aim being the development of a public        SUMMARY
     health strategy for slowing or retarding the rate of
                                                               The clinical significance of individual and / or
     cognitive decline. This may include administering
                                                               combination therapy of physical activity and cognitive
     the intervention to individuals with mild cognitive
                                                               stimulation has not been established to date in
     impairment (MCI), (often referred to as pre-clinical
                                                               the prevention of AD. The outcomes of this study
     AD), and further assess the beneficial effect of the
                                                               will throw light and provide a stepping stone in
     intervention on maintaining cognitive function and
                                                               establishing strategies for the delaying or prevention
     delaying the onset of dementia. Insight into the
                                                               of AD.
     molecular mechanisms resulting from the outcomes of
     the study may lead to novel drug therapies.

     This Project Is An Integrated Multidisciplinary
     Preventive Approach Which Includes:

     A home based physical activity and computer based
16   cognitive stimulation protocol for healthy community
     dwelling older adults.

     200 participants, aged 60-85 years, recruited for the
     study undergoing a 16 week home based program
     that includes physical activity; cognitive stimulation;
     physical activity and cognitive stimulation combined;
     or an education only group.

     Recruited participants will be assessed at baseline
     (pre-intervention), during the intervention and
     at two post-intervention time-points (16 weeks
The impact of nutrient intake on cognition in the elderly and its potential role in the
prevention of Alzheimer’s disease (AIBL study)

Due to the fact that current treatments of AD can only      protective affect or be a risk factor for Alzheimer’s
                                                                                                                       Vanessa Ward
delay symptoms by 6-12 months, and that underlying          disease (AD). I will also investigate which factors
pathologies in the brain may exist years before a           in the diet are associated with levels of blood
decline in memory is evident, it is essential that highly   biomarkers previously identified as risk factors for AD.
predictive risk factors are identified so as to intervene
and delay or prevent the onset of symptoms. Although        The project aims to assess nutrition in the complete
some risk factors have been found to increase an            AIBL cohort. The study will include analysis of dietary,
individual’s chance of developing AD, there is growing      cognitive, functional, behavioural and physical
interest that lifestyle factors may play an integral        assessments at a baseline visit and after 18 and 36
role. Manipulation of lifestyle factors, as a means         months. Levels of known AD risk factor markers which
of protecting against cognitive decline therefore,          may be affected by nutrient intake in the diet, will be
is an attractive prospect. In particular, it has been       analysed. Dietary assessment will involve analysis of
suggested that modification of intakes of nutrients in      data acquired from administration of food frequency
the diet may be an efficient and cost effective means       questionnaires. Participant responses to the
of preventing AD.                                           questionnaires are analysed for usual daily nutrient
                                                            intake and grams consumed using software based on
Nutrition has been the focus of numerous                    nutrient composition databases. The questionnaires
epidemiological studies assessing identification            will quantify intake of over 200 foods and beverages
of risk factors for AD and other chronic diseases           including focus foods for this project. e.g. red wine,
overseas, however, limited studies have been                red grapes, green tea, varieties of fish consumed.
conducted in Australia. Large-scale hallmark studies        This study will be one of the first in Australia to use
have suggested that a diet high in antioxidant rich         an online version of a questionnaire.
foods and polyunsaturated fatty acids and low in
saturated fatty acids reduces the risk of AD. Clinical      The project is of significant importance to Australia’s
trials, however, have failed to support the use of          National Research Priorities by elucidating the role of          17
supplementation of individual dietary components            dietary factors as a means of delaying the onset of AD
to reduce the risk of AD. In undertaking the project        and reducing pressure on the healthcare system.
                                                            If from 2005 the average onset of AD could be
                                                                                                                             ANNUAL REPORT 2009
                                                                                                                             ANNUAL REPORT 2009

therefore, I commenced with the hypothesis that
certain factors in the diet are associated with             delayed by 5 years, there would be a 50% reduction
cognitive outcome and known risk factor blood               in new cases each year and this would result in
biomarkers of AD. My aim is to investigate which            cumulative savings of $13.5 billion by 2020 (Access
nutritional factors in the diet are associated with         Economics, 2004).
better or worse memory, and therefore may have a
                  Combinational nutritional supplement therapies in the prevention of Alzheimer’s

                  Dr Matthew Sharman (McCusker Foundation, ECU)
                  Dr Sajla Singh (ECU)
                  Professor Ralph Martins (McCusker Foundation, ECU)

                  Significance of the project:           reduce the number of people that          potential therapies, before
                                                         are expected to develop Alzheimer’s       progressing to clinical trials in
                  Lifestyle modifications such as
                                                         disease over the next 50 years, due       humans. The development of
                  dietary interventions, and physical
                                                         to the rapidly aging population.          effective preventative strategies
                  activity programs, have long played                                              for the treatment of Alzheimer’s
                  a central role in the management       We have previously demonstrated           disease is critical if we are to
                  of several diseases such as            in an animal model of Alzheimer’s         reduce the number of people that
Dr Matt Sharman   cardiovascular disease, diabetes       disease, that both a Green Tea diet       are expected to develop Alzheimer’s
                  and cancer. It is well known that      and a Fish Oil diet were able to          disease over the next 50 years, due
                  one of the most important lifestyle    reduce the levels of beta-amyloid         to the rapidly aging population.
                  factors, diet, strongly influences     in the brain and cerebrospinal fluid.     This is an exciting approach
                  the incidence and outcome of major     However, the Fish Oil diet which is       that builds on our long term
                  age-related pathologies. Diet can      high in the omega-3 essential fatty       understanding of different
                  also strongly influence the risk of    acids resulted in significantly greater   antioxidants and beta amyloid
                  developing late-onset Alzheimer’s      reductions in beta-amyloid levels         metabolism resulting in a
                  disease, with several studies          compared to the Green Tea diet.           combination of these compounds to
                  across the world showing that          Based on these initial findings we        provide maximal synergy.
                  fruits, vegetables and fish oils are   have now begun work investigating         If successful in the current animal
                  associated with improving health       whether combinations of a                 study, it has the advantage of being
                  and decreasing an individual’s risk    number of nutritional-based-CAM           able to progress rapidly to clinical
                  for developing Alzheimer’s disease.    compounds have a greater effect           trials as these antioxidants are food
                  This is supported by research which    on reducing the pathology caused          products known to be very safe for
                  shows that low dietary intake of       by Alzheimer’s disease in an animal       human consumption.
                  fruits, vegetables and fish oils       model. Some of the compounds we
                  increase your risk for developing      are currently examining include,          This project is funded by a National
                  late-onset Alzheimer’s disease.        EGCG (a compound extracted from           Health & Medical Research Council
                  If nutritional-based complementary     Green Tea), curcumin (the main            Complementary and Alternative
                  and alternative medicine (CAM)         ingredient extracted from the spice       Medicine Strategic Grant.
                  therapies could be developed to        turmeric), DHA (one of the main
    18                                                                                             In Collaboration with
                  prevent or delay the onset for         components in fish oil) and ALA
                  Alzheimer’s disease, the impact on     (a natural antioxidant).                  A/Prof Gerald Munch
                  disease burden could be substantial.                                             (University of Western Sydney)
                  However, these CAM therapies           Major Findings to date:
                                                                                                   A/Prof Marcus Wenk
                  need to be critically evaluated        Work on this project is still ongoing,
                                                                                                   (National University of Singapore)
                  for their mechanisms, efficacy         with a number of different dietary
                                                                                                   Prof Barry Halliwell
                  and safety. The development of         combinations being trialled in
                                                                                                   (National University of Singapore)
                  effective preventative strategies      a mouse model of Alzheimer’s
                                                                                                   Prof R Vijayalakshmi
                  for the treatment of Alzheimer’s       disease. This work is critical to         (National Brain Research Institute,
                  disease is critical if we are to       establish the efficacy of these           India)
A pilot clinical study to evaluate the potential of a nutritional extract AmlamaxTM on
raising HDL levels

Dr Sajla Singh (ECU)
Dr Matthew Sharman (McCusker Foundation, ECU)
Professor Ralph Martins (McCusker Foundation, ECU)

Significance of the project:            between HDL-C levels and                    herbal Amla Extract on raising HDL-C
                                        beta-amyloid levels in 198 study            levels in population of subjects
One of the most prevalent lifestyle-    participants, providing further             with low HDL-C levels, as well
associated diseases in Western          evidence for a link between                 as to determine whether directly
society is cardiovascular disease.      cardiovascular disease and                  raising HDL-C levels can result in a
A growing body of literature also       Alzheimer’s disease. This has               decrease in plasma beta-amyloid
indicates that the presence of          suggested that strategies designed          levels. This work is being conducted
cardiovascular disease is associated    to improve cardiovascular health,           in collaboration with Arjuna Natural
with the increased risk of developing   namely raising HDL-C levels may             Extracts Ltd., a global manufacturer
late-onset Alzheimer’s disease.         protect against cognitive decline           and exporter of herbal and spice
Considerable evidence has been          and Alzheimer’s disease. While              extracts, located in Kerala, India.
provided in support of the notion       drugs that lower cholesterol and            This Amla extract, known as
that increases in total plasma          LDL-C levels are currently being            AmlamaxTM was developed by the
cholesterol, low-density lipoprotein-   considered and tested as potential          R&D lab of Arjuna Natural Extracts
cholesterol (LDL-C), and decreased      therapies for the treatment of              Limited. Amlamax is a reconstituted
high-density lipoprotein-cholesterol    Alzheimer’s disease, there are no           dry extract from fresh fruits of Amla
(HDL-C) are known risk factors          effective drugs available to raise          and has recently shown remarkable
for cardiovascular disease and          HDL-C levels - although, HDL-C              results in increasing HDL-C levels
also associated with increased          levels are known to be modified by          in patients with dyslipidemia.
Alzheimer’s disease risk.               a number of environmental factors,          However, its possible role in helping
Numerous studies have                   including diet and exercise.                to decrease Alzheimer’s disease risk
demonstrated that elevated total                                                    has not been previously explored.
plasma cholesterol results in           The Indian plant Amla (Emblica
                                                                                    The findings from this initial study
increased deposition of                 officinalis) commonly known as
                                                                                    will determine the significance of the
beta-amyloid in the brain and           Indian gooseberry has widely
                                                                                    Amla Extract in effectively treating
increases individuals risk for          been used in traditional Ayurvedic
                                                                                    patients identified with low HDL-C
developing Alzheimer’s disease.         medicine preparations for use
                                                                                    levels and its potential role in helping
Thus, one factor which may              against a variety of disease
                                                                                    to decrease the risk of developing
link cardiovascular disease and         conditions. The natural herbal
                                                                                    late-onset Alzheimer’s disease.            19
Alzheimer’s disease is HDL-C,           extract Amla has been recently
as epidemiological studies have         identified for its ability to increase      In Collaboration with
reported that high concentrations       HDL-C levels. As low HDL-C levels
                                                                                    Dr Benny Antony
                                                                                                                               ANNUAL REPORT 2009

of HDL-C or “good” cholesterol          are thought to be an important risk         (Arjuna Natural Extracts, Kerala,
(>1.5mMol/L) may also be protective     factor for late-onset Alzheimer’s           India).
against Alzheimer’s disease.            disease this has an important               Dr Binu Kuruvilla
                                        implication for future work.                (Arjuna Natural Extracts, Kerala,
Previous work performed at
the McCusker Foundation for             We have just commenced work
Alzheimer’s Research Inc., by           recently within the McCusker
Dr Kristyn Bates and colleagues         Foundation evaluating in a pilot
has demonstrated a relationship         clinical trial, the effectiveness of this
                       Other significant studies and collaborations

     Collaborations:   Collaboration has been ongoing for the last 11 years with Professor Sam Gandy from
                       Farber Institute for Neurosciences, Mount Sinai School of Medicine, New York
                       into an interdisciplinary approach to Alzheimer Drug discovery.

                       University of Adelaide & ECU Truncating presenilin mutations and their effects of
                       gamma-secretase activity, tau and beta-catenin. CIA Michael Lardelli, CIB Ralph Martins.

                       Martins R, Verdile G, (ECU) Hulse G, (UWA) Ji Tae. The role of Gonadotropins in the
                       production of Alzheimer’s beta amyloid.

                       Dementia Collaborative Research Centres on Prevention, Early Intervention
                       and Risk Reduction. Grant funded by Australian Government Dept of Health &
                       Ageing comprising Australian National University; University Melbourne; Alzheimer’s
                       Australia, Victoria; Edith Cowan University; University of Queensland.

                       Edith Cowan University, together Western Australian Dept of Health, University
                       of Western Australia and in collaboration with University of Melbourne headed
                       by Professor Colin Masters CSIRO Flagship Collaborative Research Program Detecting
                       and Preventing Alzheimer’s Disease: towards diet and lifestyle interventions.

                       “Molecular and Neuropsychological Predictive Markers of Cognitive Decline.
                       Prof. Ralph Martins, Dr Ian Martins, A/Prof. Nicola Lautenschlager. ECU & UWA.

                       Centres of Excellence in Science and Innovation Program Award funding in support
                       of the Alzheimer’s Disease Research Centre entitled Centre of Excellence for
                       Alzheimer’s Disease Research and Care. Awarded by Western Australian State
                       Government 2005. Submitted by Edith Cowan University representing partners:
                       Australian Neuromuscular Research Institute, Anglican Homes Inc. and
                       the Sir James McCusker Training Foundation, The Hall and Prior Aged Care
                       Group, Hollywood Private Hospital, The McCusker Foundation for Alzheimer’s
                       Disease Research and the University of Western Australia. State Government
                       $1.3 million and $2.6 million from participating universities.

                       Close collaboration has been established since 2004 with Dr Markus Wenk and Dr
                       RH Yang from the National University of Singapore. Project entitled “Lipodomics
                       of neuronal membranes – Identification of lipids involved in neurosecretion and
                       neurodegenerative diseases.

                       Professors Peter Hyslop and Paul Fraser from the University of Toronto to identify
                       genetic risk factors in Alzheimer’s disease. This collaboration has involved exchange
                       of students and staff between the University of Western Australia and the American
                       and Canadian institutes.
Professor Judit Miklossy from the University Institute of Pathology, University of
Lausanne in Switzerland and latterly from Center for NeuroVirology and Cancer
Biology, College of Science and Technology, Temple University, Philadelphia has
supplied 200 brain samples from post-mortem confirmed Alzheimer’s disease cases for
biochemical and genetic studies. This collaboration has resulted in several publications.

The role of oestrogen in Alzheimer’s disease is being undertaken in collaboration with
Professor Susan Craft from the University of Washington.

The structure and function of the amyloid precursor protein in Alzheimer’s disease
is being studied in collaboration with Professor Toshihara Suzuki of Hokkaido
University, Sapporo.

A study into the role of gonadotropins in the development and progression of
Alzheimer’s disease is being undertaken in a joint collaboration with Assoc. Professor
Craig Atwood from Wisconsin University Maddison Medical School, USA.

A recent collaboration has been instituted with Professor D. Allan Butterfield from the
Dept of Chemistry and Center of Membrane Sciences, University of Kentucky,
Lexington USA. This collaboration is to study oxidative stress in Alzheimer’s disease
and one of our PhD students spent six months with Professor Butterfield investigating
the protective effects of apoE isoforms on Abeta induced oxidative stress in cell culture.

Collaboration is ongoing with Associate Professor Joachim Hallmayer from Stanford
University Department of Psychiatry and Behavioural Science to identify
genetic and molecular risk factors in neurodegenerative diseases. This collaboration
has resulted in several papers.

Professor Hans Forstl from Klinik und Poliklinik fur Psychiatrie und
Psychoptherapie der Technischen Universitat Munchen, Munich, Germany
and Dr Nicola Lautenschlager from the School of Psychiatry & Clinical
Neurosciences, UWA, Dept of Old Age Psychiatry Royal Perth Hospital.
Ongoing collaboration has been established with Dr Lautenschlager and Professor Forstl
into identification of biomarkers for cognitive decline in subjective memory complainers.
                                                                                             ANNUAL REPORT 2009

Ongoing collaboration has been established with the three major research groups
working on Alzheimer’s disease in Australia led by Professor Colin Masters at the
University of Melbourne, Associate Professor Peter Schofield from the Garvan
Institute in Sydney and Professor Tony Broe from the Prince of Wales Medical
Research Institute, Sydney, New south Wales.
     Other significant studies and collaborations (Cont.)

     Dr Elizabeth Milward from the University of Newcastle New South Wales,
     ongoing research into ‘Iron-related genes and neurodegenerative disorders”.

     Collaboration is ongoing with Professor John Papadimitriou, Dr Terry Robertson
     (Department of Pathology, University of Western Australia) and Associate
     Professor Alan Harvey (Department of Anatomy, University of Western Australia)
     on the development of animal models for Alzheimer’s disease.

     Collaboration is ongoing with Professor Dharmarajan (Department of Anatomy,
     University of Western Australia) on studying the function of beta amyloid.
     This seminal work has recently been published.

     Research is ongoing with the Professor Trevor Redgrave (Department of Physiology,
     University of Western Australia) and Dr Ian Martins (ECU) who have a strong
     background in lipoprotein research. The latter collaboration is aimed at obtaining a
     better understanding of the molecular mechanism(s) by which apolipoprotein E acts
     as a major risk factor for Alzheimer’s disease.

     Professor David Bruce and Dr Bu Yeap from University of W.A. School of Medicine
     and Pharmacology, Fremantle Hospital, Effect of androgens on cognitive function
     and evolution of dementia in older men.

     Collaboration is ongoing with Professor Alan Harvey (Dept of Anatomy, University of
     Western Australia) on the development of animal models for Alzheimer’s disease.

     Collaboration has been established with Professor Leon Flicker from the Department of
     Geriatric Medicine and Professor Osvaldo Almeida from the University Department
     of Psychiatry, Queen Elizabeth II Medical Centre, to undertake an intervention study
     in patients with memory disorders.

     Collaboration has recently been established with Professor Gary Hulse, from University
22   of Western Australia’s Unit for Research and Education in Drugs and Alcohol to
     analyse the effectiveness of a therapeutic agent for Alzheimer’s disease.

West Australian State Government Award RN Martins, $2,205,000.00 over 4
years: 2010, 2011, 2012, 2013, for Discovery of biomarkers for the early diagnosis of
Alzheimer’s disease.

NHMRC 595312 Martins RN, Martins I, LaDu MJ, Sharman M, The effect of
human apoE isoforms and apoE receptors on the clearance of oligomeric A 42 by
hepatocytes in vitro $409,650 2010; 2011, 2012.

NHMRC Martins RN, Martin-Iverson M, Taddei K, Enhancing peripheral clearance
of beta amyloid as a treatment for Alzheimer’s Disease $529,125 2010; 2011, 2012.

NHMRC Equipment Grant 2008 Micro volume spectrophotometer for Alzheimer’s
and Melanoma Disease Research. Martins RN, Verdile G, Bates K, Sharman M, Lui
J, Singh S, Gupta V, Sleptsova I, Martins I, Taddei K, Foster J, Ziman M, Brown M.

NHMRC 480102 ECU Martins RN, Sharman MJ, Munch G, Wenk M, Halliwell
B, Vijayalakshmi R. Complimentary and Alternative Medicine Strategic Grants.
Evaluation of Combination Nutritional Supplement Therapies in the Prevention of
Alzheimer’s disease in a Transgenic Mouse Model. Yr 1 2009 $127,465;
Yr 2 2010 $207,869, Yr 3 2011 $149,341.

NHMRC 426406 ECU Martins R, Verdile G, Hulse G, Ji Tae. The role of
Gonadotropins in the production of Alzheimer’s beta amyloid. No salary for CIA Std
Project Grant. 3 years Yr 1 2007 $168,750; Yr 2 2008 $108,750; Yr 3 2009 $123,750

NHMRC 453622 University of Adelaide Truncating presenilin mutations & their
effects on gamma-secretase activity, tau and beta-catenin. CIA Michael Lardelli,
CIB Ralph Martins. Yr 1 2007 $118.050 , Yr 2 2008 $193,500 , Yr 3 2009 $183,500.

Neurotrauma Research Program. Foster J, Knuckey N, Martins RN, The Role of
APOE as a Modulator in Recovery from Traumatic Brain Injury. 2007 $40,000, 2008
$40,000 2009$40,000

Edith Cowan University, together Western Australian Dept of Health, University           23
of Western Australia and in collaboration with University of Melbourne headed
by Professor Colin Masters CSIRO Flagship Collaborative Research Program
Detecting and Preventing Alzheimer’s Disease: towards diet and lifestyle interventions
                                                                                         ANNUAL REPORT 2009
                                                                                         ANNUAL REPORT 2009

Total Value of Application $3,000,000.

NIH (USA) Program Grant, Prof Sam Gandy Farber Institute at Mount Sinai Medical
School, New York, Prof Jorge Ghiso, New York University, Prof. Joseph D Buxbaum
Mt Sinai School of Medicine, and Prof. Ralph Martins, University of Western
Australia and Edith Cowan University Interdisciplinary Approach to Alzheimer Drug
Discovery. Prof Martins allocation US$770,615. 4 Years 30 September 2005 – 30
September 2009.

     Foster JK, Verdile G, Bates KA, Martins RN,                  Taddei K, Laws SM, Verdile G, Munns S, D’Costa K,
     Immunization in Alzheimer’s disease: naïve hope or           Harvey AR, Martins IJ, Hill F, Levy C, Shaw JE. & Martins
     realistic clinical potential? Molecular Psychiatry (2009)    RN. Novel phage peptides attenuate beta amyloid-42
     14:239-251                                                   catalysed hydrogen peroxide production and associated
                                                                  neurotxicity. Neurobiology of Aging (2009) E-Pub ahead
     Sohrabi HR, Bates KA, Rodrigues M. Taddei K, Martins         of print. (2010) 31(2)203-214.
     G, Laws SM, Lautenschlager NT, Dhaliwal SS, Foster
     JK, Martins RN, The relationship between memory              Nornes S, Newman M, Wells S, Verdile G, Martins RN &
     complaints, perceived quality of life and mental health in   Lardelli M. Independent and co-opertive action of Psen2
     apolipoprotein Ee4 carriers and non-carriers Journal of      with Psen1 in Zebrafish embryos. Exp. Cell Res (2009)
     Alzheimer’s disease, (2009) 17(1):69-79.                     315(16): 2791-801 Accepted June 26 (Epub ahead of print)

     Bharadwaj PR, Dubey AK, Masters CL, Martins RN,              Ellis KA, Bush AI, Darby D, De Fazio D, Foster J, Hudson
     Macreadie IA. Aß aggregation and possible implication        P, Lauatenschlager NT, Lenzo N, Martins RN, Maruff P,
     in Alzheimer’s disease pathogenesis. Journal of Cellular     Masters C, Milner A, Pike Rowe, Savage G, Szoeke C,
     and Molecular Medicine. (2009) 13(3)412-21                   Taddei K, Villemagne V, Woodward M, Ames D: The AIBL
                                                                  Research Group. The Australian Imaging, Biomarkers
     Bates KA, Verdile G. Q-X Li, Ames D, Hudson P,               and Lifestyle (AIBL) study of aging: methodology and
     Masters CL and Martins RN. Clearance mechanisms              baseline characteristics of 1112 individuals recruited
     of Alzheimer’s amyloid-ß peptide: implications for           for a longitudinal study of Alzheimer’s disease INT
     therapeutic design and diagnostic tests. Feature Review      Psychogeriatr. 2009 May 27:1-16 (Epub ahead of print).
     Molecular Psychiatry (2009) 14:469-486.                      (2009) 21:627-687.
     Barron A.M., Cake M., Verdile G., and Martins RN.            Drummond ES, Harvey AR, Martins RB. Androgens and
     Ovariectomy and 17b-estradiol replacement do not alter       Alzheimer’s disease. Curr Opin Endocrinol Diabetes Obes.
     beta amyloid levels in sheep brain. Endocrinology, (2009)    (2009) June 16 (3): 254-9 Review.
                                                                  Ian J. Martins, Tamar Berger, Matthew J. Sharman,
     Chen M, Martins RN, Lardelli M. complex splicing and         Giuseppe Verdile, Stephanie J. Fuller and Ralph N.
     neural expression of duplicated tau genes in Zebrafish       Martins; Cholesterol Metabolism and Transport in
     embryos. Journal of Alzheimer’s Disease. (2009)              the Pathogenesis of Alzheimers disease, Journal of
     18(2)305-17.                                                 Neurochemistry, (2009) 111(6) 1275-308 Accepted
     Sohrabi HR, Bates KA, Rodrigues M, Taddei K, Laws
     SM, Lautenschlager NT, Dhaliwal SS, Johnston ANB,            Sudarsan Krishnaswamy, Giuseppe Verdile, David Groth,
     Mackay-Sim A, Foster JK, Martins RN. Olfactory               Limbikani Kaneyenda and Ralph N Martins; The structure
     dysfunction is associated with subjective memory             and function of Alzheimers gamma secretase enzyme
     complaints in community-dwelling elderly individuals.        complex, Critical Reviews in Clinical Laboratory Sciences,
     Journal of Alzheimer’s Disease (2009) 17(1): 135-42.         2009 46(5-6):282-301.
     Pedrini S, Thomas C, Brautigam H, Schmeidler J, Ho           Hata S. Fujishige S. Araki Y. Kato N. Araseki M.
     Lap, Fraswer P, Westaway D, Hyslop P StG, Martins RN,        Nishimura M. Hatmann D, Saftig P, Fahrenholz,
     Buxbaum JD, Pasinetti GM, Dicksterin DL, Hof PR, Ehrlich     F, Taniguchi M, Katsuya U, Akatsu H, Martins RN,
     ME, Gandy S. Dietry composition modulates brain mass         Yamamoto K, Maeda M, Yamamoto T, Nakaya T, Gandy
     and solubilizable A levels in a mouse model of aggressive    S, Suzuki T. Alcadein cleavages by amyloid B-Precursor
     Alsheimer’s amyloid pathology.                               Protein (APP) α- and γ-Secretases generate small
24   Molecular Neurodegenration (2009) 4:40.                      peptides, p3-Alcs, indicating Alzheimer’s disease-related
                                                                  γ-secretase dysfunction. Journal of Biological Chemistry.
     Bates K, Hamid R, Sohrabi H, Rodrigues M, Beilby J,
                                                                  2009 Vol 284 No. 52, 36024-36033.
     Dhaliwal SS, Taddei K, Criddle A, Wraith M, Howard
     M, Martins G, Paton A, Mehta P, Foster JK, Martins           Bourgeat P, Chetelat G, Villemagne VL, Fripp J, Raniga
     IJ, Lautenschlager N. Mastaglia F, Laws S, Gandy SE,         P, Acosta O, Szoeke C, Ourselin S, Ames D, Ellis KA,
     & Martins RN. Association of Cardiovascular Factors          Martins RN, Masters CL, Rowe CC, Salvado O and
     & Alzheimer’s Disease Plasma Amyloid-ß Protein in            the AIBL Research Group. Aß burden in the temporal
     Subjective Memory Complainers. Journal of Alzheimer’s        neocortex is related to hippocampal atrophy in non-
     Disease (2009) 17(2):305-18 Mar 56 E-Pub ahead of print.     demented elderly. Neurology (In Press).

Establishment of the plasma               The association between APOE             The AIBL Study: Baseline data from a
biomarkers for the pre-                   Levels and Alzheimer’s Disease:          multicentre, prospective longitudinal
symptomatic detection of AD:              Australian Imaging, Biomarker and        study of ageing in 1100 volunteers.
Australia Imaging, Biomarker and          Lifestyle (AIBL) Flagship Study          Ames D, Rowe C, Masters C, Martins
Lifestyle (AIBL) Flagship Study of        of Ageing. Martins RN et al. ICAD        R, Szoeke C, Hudson P, Milner A, Ellis
Ageing. Martins RN, Gupta V, Lui J,       Vienna Austria July 11-16 2009.          K. 14th International Psychogeriatric
Foster J, Taddei K, Taddei T, Brown B,                                             Association International Congress
Ward V, Rodrigues M, .Masters C. 24th     Effect of cortical placement             1-5 September 2009 Montreal
International Conference of Alzheimer’s   of luteinizing Hormone on Aß             Canada. Vol 21 Supp 2 S59-S60.
Disease Singapore 25-28 March 2009.       metabolism in guinea pigs. Wijaya
                                          LK, Wahjoepramono EJ, Taddei K,
The Role of Physical Activity on          Martins G, Howard M, Bates KA,           VISITING VIPS 2009
Blood Bio-Markers Related to              Dhaliwal SS, Verdile G, Martins RN,
Alzheimers Disease Brown BM,              ICAD Vienna Austria July 11-16 2009.     Professor Niels Andreasen,
Peiffer JJ, Taddei K, Lui J, Taddei T,                                             Karolinska Institute, Sweden.
Ward VK, Rodrigues MA, Rimajova M,        Amyloid-ß and its relevance to the
                                                                                   Professor Paul Fraser,
Foster JK, Ellis K, Masters C, Ames       detection of Alzheimer’s disease in
                                                                                   Center for Neurodegenerative
D, Hudson P, Rowe C, Martins RN           blood plasma:
                                                                                   Disease, Toronto University, Canada.
9th International AD/PD Conference        Findings from the first phase of the
                                          Australian Imaging, Biomarker and        Professor Marco Racchi,
Prague March 2009
                                          Lifestyle (AIBL) Flagship study of       University Pavia, Italy.
The role of lean body mass on             ageing.                                  Assoc. Professor MaryJo LaDu,
cognition and blood biomarkers            De Ruyck, K, Gupta V, Qiao-Xin Li,       University of Illinois, Chicago,
in a healthy control population:          Taddei K, Foster J. Taddei T, Brown B,   Jan-March 2009.
a component of the Australian             Ward C, Rodrigues M, Ellis K, Rowe       Assoc. Professor Craig Atwood,
Imaging, Biomarkers and Lifestyle         C, Villemagne V, Hudson P, Masters       University Wisconsin, Madison.
(AIBL) flagship study Peiffer JJ,         C, Martins RN, Ames D. ICAD Vienna
                                                                                   Dr Benny Antony,
Brown BM, Taddei K, Lui J, Taddei T,      Austria July 11-16 2009.
Ward VK, Rodrigues MA, Rimajova M,
                                          Establishment of the plasma              Dr Sam Burnham,
Foster JK, Ellis K, Masters C, Ames
                                          biomarkers for the pre-                  CSIRO.
D, Hudson P, Rowe C, Martins RN.                                                                                            25
9th International AD/PD Conference        symptomatic detection of AD:             Dr Victor Villemagne and
Prague March 2009                         Australia Imaging, Biomarker and         Dr Gareth Jones
                                          Lifestyle (AIBL) Flagship Study of
                                                                                                                            ANNUAL REPORT 2009
                                                                                                                            ANNUAL REPORT 2009

The AIBL Study: Baseline data             Ageing. Martins RN, Gupta V, Lui J,
from a multicentre, prospective           Foster J, Taddei K, Taddei T, Brown
longitudinal study of ageing in 1100      B, Ward V, Rodrigues M, .Masters
volunteers. Ellis K, Rowe C, Masters      C.14th International Psychogeriatric
C, Martins RN, Hudson P, Milner A,        Association International Congress
Bevege L, Ames D. 9 th International      1-5 September 2009 Montreal
AD/PD Conference Prague March             Canada. Vol 21 Supp 2 S59-S60.
                                   CliniCal Trials Division


     The Clinical Trials Division         Moderate Alzheimer Disease        Dimebon CONCERT study:
     continues to be a vital part of      Who Are Apolipoprotein E ε4       A Phase 3 Multicenter,
     the search for treatments for        Non-Carriers and carriers         Randomized, Placebo-
     Alzheimer’s disease. The trials      8 patients enrolled               Controlled, Double-Blind
     we undertake are part of an          3 early withdrawals               Twelve-Month Safety and
     international network testing the    5 ongoing patients                Efficacy Study Evaluating
     potential of drugs as treatments                                       Dimebon in Patients with
                                          GSK AZ3 study: A fixed dose       Mild-to-Moderate Alzheimer’s
     for Alzheimer’s disease. The fact
                                          study of SB-742457 versus         Disease on Donepezil
     that a small WA-based group is
                                          placebo when added to             11 patients enrolled
     considered sufficiently important
                                          existing donepezil treatment      Recruitment ongoing
     to be involved in these trials is
                                          in subjects with mild to
     testament to our efficiency and
                                          moderate Alzheimer’s              Lundbeck Lu study:
                                          disease.                          Randomised, double-blind,
     In 2008 we commenced our             5 patients enrolled               parallel-group, placebo-
     first trial of a group of drugs                                        controlled, fixed-dose study
                                          Eisai Open-Label Extension        of Lu AE58054 in patients with
     called human monoclonal
                                          Study of 23 mg Donepezil SR       moderate Alzheimer’s Disease
     antibodies. These medications
                                          in Patients with Moderate to      treated with donepezil
     may be disease-modifying. The
                                          Severe Alzheimer’s disease
     medication is given intravenously
                                          3 patients enrolled               Investigator meeting Nov 09
     as a day procedure at Hollywood
                                                                            Study commenced Nov 2009
     Private Hospital. Previously, all    A Phase 2 multicentre,            No patients enrolled in 2009
     medications were given orally or     Randomised, Double Blind,
     via an implant. We are hopeful                                         •	 Rosiglitazone
                                          Placebo-Controlled Study             670-16 enrolled/
     this medication will be effective    of the Safety, Tolerability,         675 study- 6 enrolled.
     in clearing soluble beta amyloid     and Pharmacokinetics of              Both trials closed.
     from the brain and that in turn;     multiple doses of PF-04360365
     this will have a beneficial impact                                     •	 Pfizer phase 1 study closed.
                                          in patients with Mild-to-            2 patients enrolled
     on Alzheimer’s disease               Moderate Alzheimer’s Disease
                                          3 patients enrolled and ongoing   Eli-Lilly study closed Sep
                                          Recruitment ceased                2009.
     Wyeth Bapineuzumab study:                                              2 patients enrolled and both
     A Phase 3, Multicenter,                                                withdrew early.
     Randomized, Double-Blind,                                              •	 Novartis Exelon patch study -
     Placebo-Controlled, Parallel-                                             8 patients enrolled
     Group Efficacy and Safety
     Trial of Bapineuzumab
     in Subjects With Mild to

Alzhyme Pty Limited is a               definitive diagnostic tests for       for Alzheimer’s diseases.
biotechnology company                  Alzheimer’s disease, clinical         The Company will utilise
specialising in the development        diagnosis of Alzheimer’s disease      methodology that allows the
of novel drugs and diagnostics         is primarily based on subjective      simultaneous measurement
for the effective treatment and        methods such as cognitive testing     of multiple plasma biomarkers
detection of Alzheimer’s disease.      by physicians. There remains a        from a single sample. Such a
This disease is associated with        considerable unmet market for         test would improve clinical trials
progressive memory loss and brain      a reliable, cost effective and        by facilitating better patient
cell death and mainly affects the      minimally invasive test (e.g.         recruitment, providing a more
elderly. It is estimated that about    blood test) that would allow early    accurate and earlier diagnosis of
10% of those past the age of 65        accurate diagnosis of Alzheimer’s     the disease and monitoring of drug
have Alzheimer’s disease, with risk    disease and result in improved        efficacy.
doubling every five years.             patient treatment.
                                                                             Initial studies have suggested that
The Company was formed in              The Company is now focussing          two particular blood proteins can
December 2002 out of the               on developing a blood test of         have possible roles as biomarkers
University of Western Australia        serum-based biomarkers for early      for Alzheimer’s disease. These
to commercialise the research          detection of Alzheimer’s disease.     biomarkers requires further
of Professor Ralph Martins at          These biomarkers have been            validation and are unlikely to be
the McCusker Foundation for            shown to be associated with           useful on their own right as a
Alzheimer’s Disease Research.          the onset and progression of the      diagnostic marker due to a lack
Alzhyme was established through        disease. The development of an        of specificity and sensitivity.
initial capital investment from        effective and improved diagnostic     However, these biomarkers may
its founding shareholder and           method has the potential to           be useful in a diagnostic kit when
Chairman, Mr. Harold Clough.           minimise the enormous impact          combined with a panel of 4-6 other
Alzhyme is continually seeking to      that Alzheimer’s disease will         blood biomarkers for Alzheimer’s
raise additional capital to advance    have on health, quality of life and   disease.
its pipeline of technologies through   healthcare costs in coming years.
pre-clinical development.              In addition, such a test would and    The project offers significant
                                       provide a more accurate diagnosis     commercial potential for the
Diagnostic Pipeline                    of the disease and monitoring of      early diagnosis of Alzheimer’s
                                                                             disease by allowing:                  27
In parallel to its therapeutic         drug efficacy.
program of research, Alzhyme                                                 •	 improved management of
                                       The aim of this project is to
has a pipeline of discovery                                                     clinical trials by facilitating
                                                                                                                   ANNUAL REPORT 2009
                                                                                                                   ANNUAL REPORT 2009

                                       develop a minimally-invasive,
and developmental programs                                                      better and earlier patient
                                       low cost yet reliable diagnostic         recruitment;
underway for the early diagnosis       kit for the routine detection of
of Alzheimer’s disease.                                                      •	 accurate diagnosis of
                                       Alzheimer’s disease biomarkers           Alzheimer’s disease early in
The pathological processes of          in blood serum. The Company’s            the disease course and before
Alzheimer’s disease begin many         strategy is to first determine the       significant memory loss occurs;
years before clinical symptoms         usefulness of known biomarkers
are observed. With no marketed         in blood products, followed by
                                       several other potential biomarkers
     •	 earlier and more appropriate         for the development of an early
        treatment and management of          diagnostic and imaging test for
        Alzheimer’s disease patients;        Alzheimer’s disease, using either
        identification of mild cognitive     Positron Emission Tomography
        impairment patients likely           (PET) or Single Photon Emission        The Centre of Excellence for Alzheimer’s
        to progress to Alzheimer’s           Computed Tomography (SPECT)
        disease;                                                                    Disease Research and Care (ADRC),
                                             imaging techniques.                    supported by the Western Australian
     •	 monitoring of the response to
        treatment with new amyloid                                                  Government’s Centre of Excellence in
                                             ANA-5 is being developed as a
        targeted and disease modifying                                              Science and Innovation program, is a
                                             radiopharmaceutical agent to
        therapies being developed.                                                  unique collaborative research venture
                                             image amyloid deposits in the
                                                                                    based at ECU and the McCusker
     Therapeutic Pipeline                    brains of living patients.
                                                                                    Foundation for Alzheimer’s Disease
                                             Business Strategy                      Research at Hollywood Private Hospital
     Through the research efforts
                                                                                    in Perth, WA.
     of Professor Ralph Martins, the         In January 2009 the Company
     Company has identified a family of      signed License and Option              The McCusker Foundation is a founding
     peptides that specifically neutralize   Pipeline Agreements with both          partner along with, among others, ECU,
     the damaging potential of beta-         the McCusker Foundation for            University of Western Australia, Murdoch
     amyloid in the brain. Accumulation      Alzheimer’s Disease Research and       University, Hall and Prior, Hollywood
     of beta-amyloid in the brain is         Edith Cowan University.                Private Hospital, and Amana Living.
     believed by many to be of major         This has given Alzhyme a
     importance in the pathogenesis of                                              Contact details
                                             first-right-to acquire and
     Alzheimer’s disease.                    commercialisation intellectual         Telephone: (08) 6304 5467

     The Company’s lead drug                 property in the treatment and          Facsimile: (08) 6304 5851
     candidate ANA-5 has been shown          diagnosis of Alzheimer’s disease       Email:
     to significantly inhibit beta-          arising out of either Institute and
     amyloid-induced neurotoxicity in        provides the Company with a
     several animal models and the           wonderful opportunity to increase
     Company is now moving forward,          its R & D pipeline and reduce its
28   in partnership with CSIRO, with         development risk.
     the development of an orally            By pursuing an integrated pipeline
     available analogue of ANA-5             approach encompassing diagnostic
     for the treatment of Alzheimer’s        tests, imaging agents and disease-
     disease. ANA-5 represents a             modifying drugs, Alzhyme expects to
     new and promising therapeutic           meaningfully impact the Alzheimer’s
     class of drug in development as a       disease market, ease the suffering
     treatment for Alzheimer’s disease.      of millions of patients and create a
     Because ANA-5 binds to a                future in which Alzheimer’s disease
     specific site within the human          is a treatable disease.
     beta-amyloid protein, with the          More information can be found at
     successful radiolabelling of the
     compound, the potential exists
HIGHLIGHTS FOR 2009                                       Centre of Excellence (Cont)

•	 Centre submitted final reports      6. Minster for Health Dr Kim         Presentations organised
    for six research projects to the       Hames & others                   by the Centre
    WA State Government.                   March 30th 2009.                 During 2009 Centre organised
•	 Centre researchers secured two      7. Claremont Nedlands Lions Club     following seminar series that were
    NHMRC grants totalling around          May 13th 2009.                   open to research and broader
    one million dollars.               8. Association of Independent        community:
•	 Secured another year funding            Retirees Dianella                Professor Marco Racchi –
    from ECU for Dr Simon Laws             June 3rd 2009                    University of Pavia, Italy
    who is a senior research fellow    9. Education Event Oceanic           Search of biological markers in
    in the Centre.                         Imaging, RNL Consultancy to      Alzheimer’s Disease: at the border
•	 Four new PhD students                   Medical Specialists & GP’s       between diagnostic procedures and
    commenced their studies under          June 24th 2009.                  physiopatology studies
    the supervision Prof. Ralph        10. Presentation to GP’s at          Presentation: 13 February 2009
    Martins.                               Margaret River Hospital          Professor Mary Jo LaDu –
•	 Centre researchers have                 Jul 31st.                        University of Illinois, Chicago
    completed writing a book                                                Structural and Functional
                                       11. Presentation at Voyager Wines
    aimed at the general public to                                          Interactions Among ApoE, ApoE
                                           attended by people from
    inform them of all aspects of                                           Receptors and Ab42
                                           Margaret River Region.
    Alzheimer’s disease from its                                            Presentation: 20 February 2009
                                           August 1st 2009
    history to its causes, diagnosis                                        Dr. Craig Atwood – University of
    prevention and treatment.          12. Presentation to Freemasons
                                           Burswood August 12 2009.         Wisconsin, U.S.
•	 Centre researchers published 16                                          The Reproductive-Cell Cycle Theory
    journal articles and presented     13. Presentation 31st Annual
                                                                            of Ageing
    14 research papers in various          Scientific Meeting (ANTA)
                                                                            Presentation: 27 February 2009
    national & international               Burswood August 27 2009.
                                                                            Professor Mary Jo LaDu –
    conferences.                       14. Presentation Remede, Mosman
                                                                            University of Illinois, Chicago
Invited Presentations (Director)           Park October 12 2009.
                                                                            Alzheimer’s Disease – the silent
1. Invited to speak at the             15. Presentation and Chair Pfizer    epidemic (I lose my keys – is it
    Glengarry Probus Club,                 Meeting Medical practitioners    Alzheimer’s?)
    19th January 2009.                     October 28 2009                  Presentation: 20 March 2009
2. Invited to speak at a fundraising   16. Presentation University of       Dr. Niels Andreasen – Karolinska
    film night at Margaret River           Third Age Joondalup Region.      University Hospital Huddinge,        29
    attended by over 200 people.           November 9th 2009.               Stockholm, Sweden
3. Invited to speak at the             17. Presentation Lumen Christie      Practical use of biomarkers in
    Wellmens’ Centre evening               College, Martin.                 clinical diagnostic of dementia
                                                                                                                 ANNUAL REPORT 2009

    “Let’s Talk Health” at the             November 11 2009.                Presentation: 10 November 2009
    Novatel Langley Hotel Perth,       18. Presentation Gosnells Health     Professor Paul Fraser – University
    March 23rd 2009.                       Support Group 20/11/2009.        of Toronto, Canada
4. WA Parliament House                 19. Presentation Belmont Live Life   Alzheimer’s Disease and the
    February 2nd 2009.                     Club November 26 2009.           Gamma-Secretase Complex
5. WA Parliament House                                                      Presentation: 23 November 2009
    (Treasururer, Troy Buswell, Gary
    Snook & Jim Chown.)
    February 19th 2009.
     BOARD MEMBERS, 2009

     Mr Malcolm McCusker AO QC (Patron)

     Mr Graham Nixon (Chair)                      Ms Jenny Day
     Farmer with extensive experience on boards   Chief Executive Officer of the Community
     of management.                               Development Foundation.
     Dr Terry Bayliss (Deputy Chair and           Emeritus Professor Patrick Garnett
     Representing Hollywood Private Hospital)     Former Deputy Vice-Chancellor (Research
     Manager Development Projects and             and Operations), Edith Cowan University.
     Research, Hollywood Private Hospital.
                                                  Tim Doncon
     Mr Peter Stevens (Treasurer)                 Executive Officer
     Chartered Accountant, former Company
     Director.                                    Dr Giuseppe Verdile
                                                  (Alternate Director)
     Professor Ralph Martins                      Deputy Director of Research, Post Doctoral
     (Director of Research)                       Fellow McCusker Foundation for Alzheimer’s
     Director of Research, Sir James McCusker     Disease Research.
     Alzheimer’s Disease Research Laboratory.
                                                  Board notes
     Assoc. Prof. David Groth (Representative     In accordance with the Constitution, Board
     Scientific Advisory Committee)               sitting fees are not payable to any member.
     Biomedical Science Curtin University of      No Board member sought to be reimbursed
     Technology.                                  for any expense incurred on behalf of the
     Mr Enzo Sirna AM
     President Italo–Australian Welfare and       Indemnity Insurance
     Cultural Centre                              The Foundation has indemnity insurance
30                                                cover up to $10 million in aggregate to
     Mr David McIntyre
                                                  protect funds, board members, staff
     Company Director and management
                                                  and volunteers against claims for damage
                                                  and other legal actions.
     Ms Ricky Burges                              Financial info follows
     Chief Executive Officer, West Australian
     Local Government Association.
     Ms Deborah Doncon
     Extensive experience as a CEO and
     membership of boards of management.
                                        McCUSKER ALZHEIMER’S REASEARCH FOUNDATION INC
                                                             ABN: 34 575 647 667
                                                             FINANCIAL REPORT
                                                  FOR THE YEAR ENDING DECEMBER 31, 2009

Notes To and Forming Part of the Accounts                               (e) Non Current Assets and Depreciation
                                                                        Office equipment is carried at cost, less, where applicable, any
1. Statement of Significant Accounting Policies                         accumulated depreciation. The depreciable amount of all fixed
The Board has prepared the financial statements on the basis that       assets is depreciated over the useful loves of the assets to the
the McCusker Alzheimer’s Research Foundation (Inc) is a non-            Association commencing from the time the asset is held ready
reporting entity because there are no users who are dependant           for use.
on its general purpose financial reports. This is a special purpose     All assets are depreciated over their useful lives to the Foundation
financial report prepared in order to satisfy the financial reporting   commencing from the time the asset is held ready for use.
requirements of the Associations Incorporation Act WA (1987).           The depreciation rates used for each class of depreciable assets are:
The financial statements have been prepared in accordance with          Class of Fixed Asset                             Depreciation Rate
the mandatory Australian Accounting Standards applicable to             Equipment                                        20%
entities reporting under the Associations Incorporation Act (1987)      Computer Equipment                               30%
and the significant accounting policies disclosed below, which
                                                                        (f) Impairment of Assets
the Board have determined are appropriate to meet the needs
of members. Such accounting policies are consistent with the            At each reporting date, the Board reviews the carrying values of
previous period unless stated otherwise.                                the Foundation assets to determine whether there is any indication
                                                                        that those assets have been impaired. Impairment losses are
The financial statements have been prepared on an accruals basis
                                                                        recognised in the Income Statement.
and are based on historical costs unless otherwise stated in the
                                                                        (g) Employee Benefits
notes. The accounting policies that have been adopted in the
preparation of the financial report are as follows:                     Provision is made for the Foundation’s liability for employee benefits
                                                                        arising from services rendered by employees up to balance date.
(a) Incorporation and Constitution
                                                                        Employee benefits expected to be settled within one year together
The Foundation was incorporated in accordance with the provisions       with benefits arising from wages, salaries and annual leave which
of the Associations Incorporation Act 1987 (section 9(1) on January     may be settled after one year , have been measured at the amounts
27, 2000.).Registration No A1005460A. The Constitution was              expected to be paid when the liability is settled plus related on
finalised by way of special resolution and came into effect as from     costs.
November 21, 2001. Document No 954353/15962552.
                                                                        Contributions are made by the Foundation to an employee
(b) Donations and Fundraising Income                                    superannuation fund and are charged as expenses when incurred.
Donations and fundraising monies received, by their nature can be       (h) Goods & Services Tax (GST)
recognised only when they are recorded in the books. Such items
                                                                        Revenues, expenses and assets are recognised net of the amount
as donations are brought to account on a cash basis or where they
                                                                        of GST, except where the amount of GST incurred is not recoverable
are received other than in cash, when ownership passes to the
                                                                        from the Australian Taxation Office. In these circumstances the
                                                                        GST is recognised as part of the cost of acquisition of the asset, or
(c) Cash                                                                as a part of an item of expense. Receivables and payables in the
Cash for the purposes of the Balance Sheet includes cash on hand,       Balance Sheet are shown inclusive of GST.
at bank and deposit.                                                    (i) Going Concern
                                                                        The financial statements have been prepared on a going concern
(d) Taxation The Foundation is registered with the Australian
                                                                        basis. The Foundation is dependant upon continuation of donations
Taxation Office (ATO) for both Australian Business Number (ABN)
                                                                        and fundraising income, for the pursuit of its objectives.
and Goods and Services Tax (GST). Registration ABN: 34 575 647
The Foundation is exempt from income tax under the provision
of sub-division 50.B of the Income Tax Assessment Act 1997 as
As the Foundation is for public benevolent and non-profit making the
                                                                                                                                                 ANNUAL REPORT 2009
                                                                                                                                                 ANNUAL REPORT 2009

ATO allows any donations over $2.00 as tax deductible. This was
by way of endorsement as a Deductible Gift Recipient (DGR) under
subdivision 30. BA of the Income Tax Assessment Act 1907.
                                                  BALANCE SHEET

                                                  31 December, 2009

                                                                      31 December        31 December
                                                                          2009               2008
                                                                            $                  $

      Cash on Hand                                                              800                800
      Cash at Bank                                                      1,950,130          2,612,619
      Investment – Shares at Cost                                         966,491            236,825
      Prepaid Expenses                                                      10,420               6,574
      Accrued Income                                                        16,076             50,907
      Other Receivables                                                    147,229             26,087
                                                                        -------------      -------------
     TOTAL CURRENT ASSETS                                              3,091,146          2,933,812
                                                                       -------------      -------------
                                                                          161,348           190,438
      Plant & Equipment                                                 -------------     -------------
                                                                          161,348           190,438
     TOTAL NON-CURRENT ASSESTS                                          -------------     -------------
                                                                       -------------       ------------
     TOTAL ASSETS                                                      3,252,494          3,124,250
                                                                       -------------       ------------

      Trade Creditors                                                      256,643            308,405
      Other Creditors                                                         5,559               8,615
      Provision for Employee Leave Entitlements                              14,998             13,947
                                                                         -------------      -------------
     TOTAL CURENT LIABILITIES                                              277,200            330,967
                                                                         -------------      -------------

      Provision for Employee Leave Entitlements                              13,575             11,239
      Loan                                                                   50,000             50,000
                                                                         -------------      -------------
     TOTAL LONG TERM LIABILITIES                                             63,575             61,239
                                                                         -------------      -------------
     TOTAL LIABILITIES                                                     340,775            392,206
                                                                         -------------      -------------
                                                                         $ 2,911,719        $ 2,732,044
     NET ASSETS                                                                             ========

     EQUITY                                                             2,000,000          2,000,000
      Endowment Reserve                                                                      732,044
      Retained Earnings                                                                    -------------
                                                                         $ 2,911,719       $ 2,732,044
     TOTAL EQUITY                                                       ========           ========
                                  DETAILED PROFIT & LOSS STATEMENT

                                     For The Year Ended 31 December, 2009

                                                                            31December         31December
                                                                               2009               2008
                                                                                 $                  $

 Donations – General                                                             174,799            134,234
 Donations – Major (>$5,000)                                                    454,490             778,495
 Fundraising & Events                                                             16,420               1,982
 Lions Club of WA                                                                  2,894             35,032
 Scrap – It Income                                                                 2,500              37,977
 Interest                                                                         88,130            199,463
 Investment Income                                                               137,175                     -
 Sundry Income                                                                           -             6,341
 Research                                                                        110,000              14,911
 Clinical Trials Income                                                         484,551             264,306
                                                                             -------------       -------------
TOTAL INCOME                                                                    1,470,959           1,472,741
                                                                             -------------       -------------

 Accounting / Audit Fees                                                            2,776                  -
 Advertising                                                                          223             1,907
 Bank Fees                                                                          1,788             1,895
 Centre of Excellence                                                             50,000             50,000
 Cleaning                                                                           6,529                  -
 Computer / Internet Expenses                                                     13,821             12,039
 Consulting Fees                                                                  44,723             49,015
 Depreciation                                                                     53,487             65,099
 Electricity                                                                          790               544
 Entertainment                                                                      1,559                  -
 Fundraising & Conference                                                                -           26,263
 Insurance                                                                        15,266             10,982
 Laboratory Expenses                                                                6,363            33,554
 Leasehold Improvements W/off                                                            -           11,231
 Medical Procedures                                                               54,254             50,837
 Office Equipment & Expenses                                                      13,790                   -
 Postage, Printing & Stationery                                                   41,340             27,754
 Professional Services                                                            19,346             12,500
 Promotions                                                                              -           14,076
 Rent & Outgoings                                                                 78,097             26,296
 Repairs & Maintenance                                                              1,500            1,745
 Research                                                                         101,117                 -
 Salaries & Wages                                                                725,470           562,452
 Staff Amenities                                                                      859                 -
 Staff Expenses - Other                                                             6,701           11,791 33
 Superannuation                                                                    17,702            16,221
 Sundry Expenses                                                                    3,540             4,100
 Telephone                                                                        18,320              2,219
                                                                                                                 ANNUAL REPORT 2009
                                                                                                                 ANNUAL REPORT 2009

 Travel & Accommodation                                                            11,923                  -
                                                                              -------------     -------------
 TOTAL EXPENSES                                                               1,291,284           992,520
                                                                             --------------     -------------
 Operating Profit                                                             $ 179,675         $ 480,221
                                                                            ========          =========
                                              STATEMENT OF INCOME AND EXPENDITURE

                                                     For The Year Ended December 31, 2009

                                                                                31 December        31December
                                                                                    2009              2008
                                                                                      $                 $

     Total Income                                                                 1,470,959          1,472,741

     Total Expenditure                                                          ( 1,291,284)         ( 992,520)
                                                                                   -------------     -------------
     Surplus of Receipts over Expenditure                                            179,675           480,221

     Income Tax Expense                                                                       -                  -
                                                                                  -------------      -------------
     Surplus From Ordinary Activities After Income Tax Expense                      179,675            480,221

     Retained Earnings at Beginning of Year                                        732,044            251,823
                                                                                 -------------      -------------
     Retained Earnings at End of Year                                             $ 911,719         $ 732,044
                                                                                ========           ========

                                                 Notes To and Forming Part of the Accounts

                                                                                    2009                                           2008
                                                                                      $                                              $
2. Cash at Bank
Business Cheque Accounts
Bank account – BNZA                                                              414,179                                        128,057
Bank account – NAB                                                               122,567                                          9,673
Bank account – NAB Clinical Trials                                                53,384                                              -
Term Deposits
National Australia Bank                                                        1,000,000                                      1,473,808
ANZ                                                                                        -                                  1,003,131
MacQuarie                                                                        360,000                                                  -
Nulsen Haven Account                                                                       -                                     ( 2,050)
                                                                              --------------                                 --------------
                                                                               1,950,130                                      2,612,619
                                                                              --------------                                ---------------
3. Plant and Equipment
Research Equipment at Cost                                                     523,570                                          499,173
Less Accumulated Depreciation                                                (365,700)                                         (315,137)
                                                                            --------------                                   --------------
                                                                                157,870                                         184,036
                                                                            --------------                                   --------------

Computer Equipment at Cost                                                      25,690                                           25,690
Less Accumulated Depreciation                                                  (23,475)                                         (21,324)
                                                                            --------------                                   --------------
                                                                                   2,215                                           4,366
                                                                           ---------------                                  ---------------

Furniture and Fittings at Cost                                                    3,656                                            3,656
Less Accumulated Depreciation                                                    (2,393)                                          (1,620)
                                                                            --------------                                   --------------
                                                                                  1,263                                            2,036
                                                                            -------------                                    -------------
Total                                                                          $ 161,348                                        $ 190,438
                                                                             ========                                       =========

4. Payables
Current                                                                        256,643                                         308,405

Other Creditors                                                                   5,559                                            8,615

Employee Holiday Pay Provision                                                  14,998                                           13,947
                                                                            -------------                                    -------------
                                                                               $ 277,200                                        $ 330,967
Non Current
Loan – Unsecured, Non Interest Bearing                                          50,000                                           50,000
Employee Long Service Leave Provision                                            13,575                                           11,239
                                                                             -------------                                    -------------
                                                                                                                                              ANNUAL REPORT 2009
                                                                                                                                              ANNUAL REPORT 2009

                                                                               $ 63,575                                         $ 61,239
                                                                             ========                                          =======

5. Contingencies
The Foundation has no known contingent liabilities or capital commitments at reporting date.
6. Events Occurring After Balance Date
There has been no material or significant events subsequent to 31 December, 2009 which have materially affected the operations or the
financial position of the Foundation.
                                                            STATEMENT BY THE BOARD

     The Board has determined that the Foundation is not a reporting entity and that this special purpose financial report should be prepared in
     accordance with the accounting practices outlined in the Notes to and Forming Part of the Financial Statements.
     In the opinion of the Board, the Financial Report:
     (a) Presents the financial position of the McCusker Foundation for Alzheimer’s Research Inc. at 31 December, 2009 and its performance for
         the year ended on that date; and
     (b) At the date of this statement there are reasonable grounds to believe that the Foundation will be able to pay its debts as and when they
         fall due.
     This statement is made in accordance with a resolution of the Board and is signed for and on behalf of the Board by:

     _________________________                                                                        ____________________________
     Graham Nixon                                                                                     Tim Doncon
     Chairman                                                                                         Executive Officer

     Dated: 23rd March, 2009

McCusker Alzheimer's
Research Foundation Inc
184 Hampden Rd, Nedlands WA 6009
Tel:   +61 8 9347 4203
Fax: +61 8 9347 4299

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