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2018 Alzheimer's Association Research Grant (AARG)

Effect of chronic sleep disruption on brain tau phosphorylation and spread

Does sleep disruption lead to more rapid build-up of abnormal tau protein in the brain?

Andrew Varga, M.D., Ph.D.
Icahn School of Medicine at Mount Sinai
New York, NY - United States


Research studies have revealed that sleep disruption may increase the risk of developing Alzheimer’s and other brain diseases. It is as yet unclear how sleep is connected to these brain changes, such as the accumulation and spread of an abnormal form of the protein tau. A characteristic of these diseases is the formation of tangles of abnormal tau proteins in the brain that interferes with food transport to the nerve cells and thereby affects the nerve cell function. For instance, in the earliest stages of Alzheimer’s, tau has been shown to accumulate in a special brain region important for regulating sleep.

Research Plan

Dr. Andrew Varga will test the possibility that sleep disruption accelerates the accumulation and spread of abnormal tau protein in the special brain region. The researchers will use two different types of mice- 1) one that develops tangles of abnormal tau in all the brain regions and 2) the other that develops tau tangles only in the special brain region that is important for sleep. Dr. Varga hypothesizes that compared to normally sleeping mice, the mice that experiences chronic sleep disruption might experience faster accumulation of tau. Using the second mice model, the researchers plan to characterize where tau spreads in the brain and the time course over which it occurs. Dr. Varga will then determine whether chronic sleep disruption changes where and when tau spreads from the special brain region in the mice model.


Studies suggest that sleep is critical for overall health—sleep disorders and disrupted sleep have been linked to various health issues. Understanding how disrupted sleep affects the development of Alzheimer’s and other brain diseases may lead to lifestyle recommendations that could help slow the onset and progression of these brain diseases.

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