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Aarkstore.com - Alzheimers Disease Biomarkers in Cerebrospinal Fluid and Blood_ 2011

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   Alzheimers Disease Biomarkers in Cerebrospinal Fluid and
                         Blood, 2011
http://www.aarkstore.com/reports/Alzheimers-Disease-Biomarkers-in-Cerebrospinal-Fluid-and-Blood-
2011-146443.html

Summary

This report provides an overview of biomarkers associated with Alzheimer’s disease (AD) found in
cerebrospinal fluid and blood, that have potential in differential diagnosis, in following treatment, in
clinical trials and drug discovery.

AD biomarkers offer utility in a number of ways: identification of groups at risk of developing AD;
early detection of AD; differentiation of different forms of neurodegenerative disease from AD, as well
as developmental stages (such as MCI), thought to progress to AD; supporting specific treatments or
pharmacological interventions; following the time-course progression of AD and response to therapy;
assessing patient prognosis; advancing understanding of the disease, including risk factors, and the
changes that precede its development; the identification of new drug targets and candidate molecules;
development of discovery assays for efficacy or toxicity markers; and supporting the recruitment of
subjects most likely to provide a meaningful analysis of treatment effects. These areas are, therefore,
considered and discussed in relation to the AD biomarkers presented in this report.

Of the biomarker areas being researched, the goal of developing methods for the early detection of
AD, including the prediction of risk in particular patient groups, is a key priority. It is believed that the
first symptoms of AD – generally diagnosed using cognitive, behavioural and functional assessments –
occur after significant neuronal loss has already occurred. Consequently, it is thought that patients
diagnosed at this stage will be less likely to gain benefits from treatment. This also hampers the
development of disease-altering therapies, because, without adequate comparators (e.g. showing
those who have the disease, or a particular developmental stage such as MCI, compared to healthy
controls), it is difficult or impossible to evaluate treatment effects. Therefore, in the preparation of this
report, emphasis was given to identifying biomarkers with potential in the early detection of the
disease, or alternatively, in differentiating different stages or types of neurodegenerative disease,
thought to be related to AD.

This Report

There are many AD biomarker studies; a report of this nature can provide only a general overview.
More than 750 studies have been reviewed in its preparation (up to January 2011), and the findings
from a short-list of approximately 150 studies are presented and discussed. The key goals of this
report are practical in nature – to identify biomarkers that show the greatest potential in advancing
research and development in the diagnosis and treatment of AD. The goals are as follows:
a) to review studies published over the last decade (up to Jan 2011) for short-listing;
b) to identify controlled clinical studies relating to AD and/or neurodegenerative conditions or stages
believed to precede AD (e.g. MCI), that included the study of biomarkers (blood, CSF, genetic, image-
based and others NB: this report presents only those findings relating to CSF and blood); and
c) to short-list opportunities to develop tests in the areas of utility indicated, with a particular
emphasis on the early detection of AD or following disease progression.

Significant advances in this field have occurred in recent years. While considerable effort has focused
on Abeta and tau related markers, a substantial number of other molecules and parameters have been
identified, that may offer opportunities. Increasingly, correlations are also being seen between
different types such as imaging and species found in CSF. This report identifies 58 candidate AD
biomarkers and their associated studies. These were identified in CSF (40) and blood (18).
Approximately 30 percent of these were linked with the early detection of AD.

Table of Contents:

Index Page
Chapter 1 Background 18
1. Alzheimer’s Disease 19
1.1 Statistics and Costs 19
1.2 Histopathology 20
1.3 Amyloid Beta (Abeta) 20
1.4 Tau Proteins and Neurofibrillary Tangles 21
1.5 Cholinergic Hypothesis 22
1.6 Diagnosis 22
1.7 Cognitive Tests 23
1.8 Stages of Alzheimer’s Disease 25
1.9 Treatment of AD 25
1.10 Biomarkers 26
1.11 Genetics 27

Chapter   2   CSF Biomarkers and Diagnosis 33-47
Chapter   3   Blood Biomarkers and Diagnosis 52-62
Chapter   4   CSF Biomarkers and Early Detection 65-75
Chapter   5   Blood Biomarkers and Early Detection 74-80
Chapter   6   Discussion 83-89

Table 2.1 CSF biomarkers associated with the diagnosis of Alzheimer’s Disease, once it has developed

Table 3.1 Blood biomarkers associated with the diagnosis of Alzheimer’s Disease, once it has
developed

Table 4.1 CSF biomarkers associated with the diagnosis of early-stage Alzheimer’s Disease

Table 5.1 Blood biomarkers associated with the diagnosis of early-stage Alzheimer’s Disease

Table 6.1 Blood biomarkers associated with the diagnosis of Alzheimer’s Disease, once it has
developed

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