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2017 Grants - Walsh
A Blood-Based Molecular Fingerprint for Early Alzheimer's Disease
Dominic Martin Walsh, Ph.D.
Brigham and Women's Hospital
2017 Zenith Fellows Award
Can a blood test be used to detect and diagnose Alzheimer's disease?
Currently, there is an extensive research effort aimed at finding ways to prevent or treat Alzheimer's disease. It is widely recognized that successful approaches will require detecting and diagnosing the disease in its earliest stages, so that treatments can be started when nerve cells are still viable. Therefore, another important focus of research is the development of reliable and simple ways to diagnose Alzheimer's disease in its earliest stages.
Two biomarkers that have been studied for possible use in diagnosis are the protein tau and the protein fragment beta-amyloid. These two biomarkers are involved in Alzheimer's-related changes in the brain, and both can be measured in the blood and the cerebrospinal fluid (CSF). The CSF is the fluid that surrounds the brain; its use for routine diagnosis is problematic because the procedure to collect samples is highly invasive. Blood samples are easier to obtain, but studies using tau or beta-amyloid measurements from blood samples have had only limited success for diagnosing disease.
Dominic Martin Walsh, Ph.D., and colleagues have proposed a series of studies with the goal of developing a reliable and sensitive test for Alzheimer's disease using blood samples. In previous studies, researchers measured beta-amyloid in whole blood. However, beta-amyloid occurs in three different components of the blood, and there is evidence that measuring beta-amyloid in specific fractions of the blood, not whole blood, will yield more useful results. Therefore, Dr. Walsh and colleagues have developed novel biochemical methods for separating the three states of beta-amyloid in blood.
The researchers propose to measure each of these fractions of blood for beta-amyloid in groups of people with or without Alzheimer's. They will also perform the same tests in blood samples collected at different times during disease onset and progression, in order to understand how blood levels change during disease progression. Because levels of tau in blood have not been studied in detail, Dr. Walsh's team will perform similar studies to determine if tau can also be used as a diagnostic marker of Alzheimer's disease.
These studies will provide valuable information that could lead to the development of a relatively non-invasive, more accurate, and reliable test for diagnosing and monitoring Alzheimer's disease in both individuals who are non-symptomatic or symptomatic. This ability will not only help diagnose individuals, it will also accelerate the development of new treatments by allowing clinical trials to enroll people more accurately diagnosed with the disease or at earlier stages when individuals would see the most benefit.