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2016 Grants - Chen
Identification of Cellular Factors that Control Tau Aggregation and Spread
John Jerry Chen, Ph.D.
University of California, San Francisco
San Francisco, California
2016 Alzheimer’s Association Research Fellowship (AARF)
What genes and proteins contribute to the build-up of tau tangles throughout the brain as Alzheimer’s disease progresses?
Tau is a protein that normally functions as part of the nerve cell structure and to help transport nutrients. In Alzheimer’s disease, however, tau becomes abnormally modified and can accumulate into tau tangles in the brain, a hallmark of the disease. Tau tangles are thought to contribute to nerve cell dysfunction in Alzheimer’s and other neurodegenerative diseases. Recently, scientists have discovered that abnormal tau may be able to move from one nerve cell to another, suggesting this may be one mechanism by which changes associated with Alzheimer’s progress across different brain regions. The cellular factors that control this process are not yet understood.
John Jerry Chen, Ph.D., and colleagues have proposed a series of experiments to better understand the molecular mechanisms that underlie the accumulation and movement of tau throughout the brain. Using nerve cells growing in laboratory dishes, the researchers can visualize the development of tau tangles using a special dye. The researchers will then use a new molecular technique to turn specific genes on or off and measure how this affects the ability of tau to form tangles or to spread to other cells. The researchers will also identify the specific proteins that bind to tau and affect these processes.
These studies could shed new light on the biochemical pathways, genes and proteins that contribute to the formation of tau tangles throughout the brain as Alzheimer’s disease progresses. The results of this work may lead to the development of new drugs that target this process to help slow or prevent Alzheimer’s disease.