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2014 Grants - Musiek
The Circadian Clock as a Therapeutic Target for Alzheimer’s Disease
Erik Musiek, Ph.D.
Washington University School of Medicine
St. Louis, Missouri
2014 New Investigator Research Grant
Circadian rhythms are biological changes that occur in animals and plants over an approximately twenty-four hour cycle. These changes usually respond to the amount of light and darkness in an environment, and involve daily patterns of sleeping, eating and other processes. Circadian rhythms are controlled by genes and proteins that make up the body’s “circadian clock.” For people with Alzheimer’s disease, these genes and proteins tend to become dysfunctional — promoting sleep disorders and other problems associated with the disease. However, the causes of circadian dysfunction and the effects it may have on Alzheimer’s disease progression are not well understood.
In preliminary studies, Erik Musiek, Ph.D., and colleagues engineered mice to lack a key circadian clock gene. These mice experienced several brain changes associated with Alzheimer’s disease, including brain inflammation, brain cell damage and increased levels of beta-amyloid, a protein which can form amyloid plaques, a hallmark of Alzheimer’s disease. Based on these results, the researchers hypothesize that circadian clock genes may protect the health of brain cells, in part, by regulating beta-amyloid production.
For their current grant, Dr. Musiek and colleagues will test these theories using mice engineered to develop Alzheimer’s-like brain changes. Some of the mice will also be engineered to lack certain circadian clock genes, while others will be placed in environments with abnormal exposure to light and darkness using a method that mimics jetlag. Both techniques will alter the animals’ circadian rhythms in specific ways. The researchers will then measure changes in sleep patterns, beta-amyloid levels, brain inflammation and other Alzheimer’s-related factors. In other studies, they will enhance the circadian clock function in mice engineered to develop Alzheimer’s-like brain changes to determine whether this therapy may protect against the disease-related effects of beta-amyloid. The study’s results could reveal more about how circadian dysfunction is linked to Alzheimer’s disease and could possibly identify novel therapies to target circadian systems for the prevention or treatment of Alzheimer’s disease.