Abstract
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Researchers at Washington University School of Medicine in St. Louis have identified a brain protein known as YKL-40 that may link Alzheimer's disease with dysfunction in circadian rhythms, suggesting that treatments that target the protein could slow the course of the disease.
“People have been measuring YKL-40 in spinal fluid for several years, but we were never sure of its function, if it was good or bad,” said Erik Musiek, M.D., Ph.D., an associate professor of neurology and senior author of the paper. “Our data suggest that in Alzheimer's, it's bad. People who have less of it fare better. If you could design a therapy to lower YKL-40, it might help the microglia remove more amyloid and maybe slow the progression of disease.”
Our daily rhythms are set by a master clock in the brain that is driven by the day and night cycle. Fractured sleep, daytime sleepiness, and other signs of disturbance in the body's circadian rhythm are common complaints among people with Alzheimer's disease, and the problems only get worse as the disease progresses. However, to date, the reason for this link between Alzheimer's and circadian dysfunction hasn't been well understood.
“If your circadian clock is not quite right for years and years—you routinely suffer from disrupted sleep at night and napping during the day—the cumulative effect of chronic dysregulation could influence inflammatory pathways such that you accumulate more amyloid plaques,” said Musiek. Amyloid plaques in the brain are one of the early hallmarks of Alzheimer's disease. “We hope that a better understanding of how the circadian clock affects YKL-40 could lead to a new strategy for reducing amyloid in the brain.”