Alzheimer's Disease Biomarkers in Cerebrospinal Fluid and Blood
2011
| Product Code | BPR00005 |
| Publication Date | February 2011 |
| Publisher | BioPharm Reports |
| Product Type | Report |
| Pages | 89 |
| ISBN Number | not applicable |
Alzheimer's Disease Biomarkers in Cerebrospinal Fluid and Blood
2011
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.
Contents
Chapter 1 Background 181. 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
Table 6.2 Blood biomarkers associated with the detection of early-stage Alzheimer’s Disease
Table 6.3 CSF biomarkers associated with the diagnosis of Alzheimer’s Disease, once it has developed
Table 6.4. CSF biomarkers associated with the diagnosis of early-stage Alzheimer’s Disease