Researchers at Washington University School of Medicine in St. Louis report that amyloid pathology in mouse models of Alzheimer’s disease disrupts circadian rhythms in microglia and astrocytes, altering the timing of hundreds of genes. Published October 23, 2025, in Nature Neuroscience, the study suggests that stabilizing these cell-specific rhythms could be explored as a treatment strategy.
Alzheimer’s disease often unsettles daily patterns early on, with nighttime restlessness and daytime napping common; in advanced stages, many patients experience “sundowning,” or heightened confusion in the evening. These clinical rhythms point to a link between the disorder and the body’s circadian system, which governs sleep–wake cycles and other biological processes.
In a study from Washington University School of Medicine in St. Louis, scientists used mouse models to probe that connection. The team found that amyloid buildup—a hallmark of Alzheimer’s—disrupted normal day–night patterns of gene activity in two types of glial cells, microglia and astrocytes, which support brain health and immune defense. The findings were published October 23, 2025, in Nature Neuroscience.
To capture how gene activity changes across the day, researchers collected cortical tissue every two hours over a 24-hour period from mice engineered to develop amyloid plaques, from healthy young mice, and from older mice without plaques. The analysis showed that amyloid pathology scrambled the timing of hundreds of genes in microglia and astrocytes. Many of the affected genes help microglia clear debris—including amyloid—suggesting that loss of coordinated timing may impair this cleanup function.
“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 Washington University, who led the study. Prior work from his group indicates that sleep disturbances can precede memory loss by years, and the stresses caused by disrupted sleep may contribute to disease progression.
The team also observed that amyloid appeared to induce new daily rhythms in genes not typically under circadian control, many linked to inflammation and stress responses. Musiek, who co-directs the Center on Biological Rhythms and Sleep, said the results point to potential therapies aimed at strengthening or tuning circadian clocks within specific cell types. “We have a lot of things we still need to understand, but where the rubber meets the road is trying to manipulate the clock in some way,” he said.
The research was supported by the National Institute on Aging, the National Institute of Neurological Disorders and Stroke, and the National Institutes of Health.
