Alzheimer's disrupts circadian rhythms of plaque-clearing brain cells

Summary

Visit the News Hub Alzheimer’s disrupts circadian rhythms of plaque-clearing brain cellsMouse study shows how disease reprograms genes in specialized cells involved in amyloid removalGetty ImagesIn a study published in Nature Neuroscience, researchers at WashU Medicine found in mice that amyloid accumulations in the brain — which are characteristic of Alzheimer’s disease — threw off the daily rhythms of hundreds of genes in brain cells known as microglia and astrocytes in ways that were different from what aging alone caused. Alzheimer’s disease is notorious for scrambling patients’ daily rhythms. Restless nights with little sleep and increased napping during the day are early indicators of disease onset, while sundowning, or confusion later in the day, is typical for later stages of the disease. These symptoms suggest a link between the progression of the disease and the circadian system — the body’s internal clock that controls our sleep and wake cycle — but scientists did not know the full nature of the connection. Researchers from Washington University School of Medicine in St. Louis have now shown in mice that the circadian rhythms within particular brain cells are disrupted in Alzheimer’s disease in ways that change how and when hundreds of genes regulate key functions in the brain. The findings, published October 23 in Nature Neuroscience, suggest that controlling or correcting these circadian rhythms could be a potential way to treat the disease. “There are 82 genes that have been associated with Alzheimer’s disease risk, and we found that the circadian rhythm is controlling the activity of about half of those,” said Erik S. Musiek, MD, PhD, the Charlotte & Paul Hagemann Professor of Neurology at WashU Medicine, who led the study. In mice modeling Alzheimer’s disease, the typical daily activity patterns of those genes were altered. “Knowing that a lot of these Alzheimer’s genes are being regulated by the circadian rhythm gives us the opportunity to find ways...