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2015 Grants - Shi
Tau Efflux via Exosomes and Potential Plasma Biomarker of Alzheimer’s Disease
Min Shi, Ph.D.
University of Washington
2015 New Investigator Research Grant
Can the study of exosome activity lead to a novel blood test for Alzheimer’s disease?
Tau protein normally plays a vital role in maintaining nerve cell structure. In Alzheimer’s disease, however, tau molecules accumulate into toxic neurofibrillary tangles which can hinder nerve cell communication and eventually lead to nerve cell death. Thus, an important focus of Alzheimer’s research is to find therapeutic ways of clearing harmful tau from the brain. One way in which nerve cells remove tau build-up is by transporting it out of the cell using specialized “cargo-carrying” compartments called exosomes. Under normal conditions, exosomes may ensure that abnormal proteins are cleared from the brain into the blood. In Alzheimer’s this process may become dysregulated leading to the accumulation of abnormal tau inside nerve cells.
In initial studies Min Shi, Ph.D., and colleagues developed a novel method for isolating exosomes from the blood that had originated from the brain. They found that in blood samples from people with Alzheimer’s disease, such exosomes contained significantly lower levels of tau when compared to those from healthy people. This finding indicates that tau accumulation in Alzheimer’s may occur, in part, because the brain loses its ability to release unwanted tau into the blood via exosomes. For their current grant, the researchers will study Alzheimer’s-like mice to determine if the clearance of tau from the brain via exosomes is impaired, resulting in tau accumulation and subsequent nerve cell damage. They hope to identify the precise forms of tau that are most likely to be transported, and determine how such transport becomes altered in Alzheimer’s disease. The team will also measure tau levels in exosomes isolated from the blood of people with and without Alzheimer’s disease and determine whether this can be used to accurately differentiate the two participant groups.
If successful, this study could shed new light on how abnormal tau accumulates in the brain in Alzheimer’s disease. It could also lead to the development of a novel and inexpensive blood test for diagnosing Alzheimer’s at its earliest stages — or for monitoring the progression of the disease in people who have Alzheimer’s.