The Circadian Clock Modulates Neurodegeneration in Alzheimer’s Disease Via REV-ERBA (Year 1)


The circadian clock controls 24-hour rhythms in the body and serves as an important regulator of brain function. Recent evidence suggests that disturbances in circadian function, which are common in our modern society, can promote Alzheimer’s disease. People with AD often exhibit symptoms of circadian dysfunction, such as disrupted sleep at night and excessive daytime napping—and subtle circadian changes can be detected in people with AD-related changes in the brain years before the onset of memory symptoms. Circadian rhythms are generated by the function of specific circadian clock genes, which are expressed in most cells of the body. Disrupting these clock genes can cause inflammation or damage in the brain of mice. A specific clock gene, REV-ERBα, seems to regulate brain inflammation. This research will investigate the functions of REV-ERBα in the brain, and determine molecular mechanisms by which it may influence neurodegeneration. Novel drugs that activate REV-ERBα will be used to see whether this might have protective effects in a mouse model of AD. The research goal is to understand exactly how circadian dysfunction promotes AD, and to use novel therapies to directly activate certain clock genes to prevent neurodegeneration.


Funding to Date



Studies of Alternative Neurodegenerative Pathways, Translational


Erik S. Musiek, M.D., Ph.D.