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Wednesday, July 16, 2014

Biomarkers and Further Progress on a Blood Test for AD

Dear Readers,

Many of you have read or heard the term Biomarker. In this blog, I would like to review a recent discovery in AD biomarkers and provide the context for its meaning and potential value. A biomarker may be measured in a sample (as a blood, urine, or biopsy), it may be a recording obtained from a person (blood pressure, ECG), or it may be an imaging test (brain MRI or echocardiogram.

Biomarkers can indicate a variety of disease characteristics. For example, they can indicate the level of exposure to a toxic environmental factor, such as lead levels in the blood; or the presence of cancerous cells, such as in a pap smear looking for cervical cancer; or the genetic susceptibility for a disease, such as the BRCA1 DNA mutation for breast cancer. Thus, a simple way to think about and classify biomarkers is as 1) indicators of disease risk 2) indicators of disease state (is the disease present), or 3) indicators of disease rate (progression). One of the best known biomarkers is LDL cholesterol and the risk it imparts for heart disease.

A commonly used analogy when discussing biomarkers for Alzheimer’s disease is that of cancer. An individual may have a biomarker that indicates increased risk for breast cancer: positive BRCA1 gene mutation. Years later, that individual might have an abnormal mammogram showing a small tumor (disease state), and if left untreated she might develop metastatic disease with tumors in the lungs as seen by PET scan (disease progression.

In Alzheimer’s dementia, a genetic mutation, such as PSEN1 is a biomarker that indicates increased risk for developing AD. A positive amyloid PET scan can indicate presence of amyloid plaques (indicating increased risk and disease state). Finally, an MRI demonstrating brain atrophy, or shrinkage, can indicate neurodegeneration (which shows disease progression). A major effort in the field has been to find an accurate, reliable, practical and inexpensive biomarker for AD. The discovery of a blood test for AD would truly represent a watershed moment in the field, and likely be second in importance only to the discovery of a disease modifying drug.

In the most recent development, a paper published last week in the journal Alzheimer’s and Dementia, described a panel of 10 proteins in the blood. The researchers looked at blood samples from 1,148 subjects: 476 with AD dementia, 220 with MCI, and 452 elderly controls with no dementia. The researchers have identified a panel of plasma biomarkers that correlate closely with other biomarkers of AD, specifically, neuroimaging measures of disease and cognitive measures of memory functioning. Moreover, the 10 protein biomarkers can accurately predict disease conversion from MCI to AD dementia within a year of blood sampling. At the AAIC meeting in Copenhagen we have heard about a retinal measure of amyloid as a potential biomarker, as well as a simple smell test, which also seems to correlate with AD pathology in the brain.

As with other biomarker studies, we need to better understand if this protein panel, retinal scan and smell test will serve as an indicators of disease risk, disease state and disease progression. However, with this recent work, we are getting much closer to that possibility.

Thanks for reading,

Michael Rafii, MD, PhD
Director, Memory Disorders Clinic
Medical Core Director
Alzheimer’s Disease Cooperative Study
University of California San Diego
Author: Michael Rafii MD,PhD at 8:56 AM 0 Comments

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The Alzheimer's Disease Cooperative Study (ADCS) was formed in 1991 as a cooperative agreement between the National Institute on Aging (NIA) and the University of California, San Diego. The ADCS is a major initiative for Alzheimer's disease (AD) clinical studies in the Federal government, addressing treatments for both cognitive and behavioral symptoms. This is part of the NIA Division of Neuroscience's effort to facilitate the discovery, development and testing of new drugs for the treatment of AD and also is part of the Alzheimer's Disease Prevention Initiative.

The ADCS was developed in response to a perceived need to advance research in the development of drugs that might be useful for treating patients with Alzheimer's disease (AD), particularly drugs that might not be developed by industry.