Alzheimer's Disease Disrupts Circadian Rhythms, Threatening Brain Function

Researchers at Washington University School of Medicine in St. Louis have discovered that Alzheimer's disease disrupts the circadian rhythms of brain cells involved in clearing amyloid plaques, a hallmark of the neurodegenerative disease. The study, published in Nature Neuroscience, found that amyloid accumulations in the brain throw off the daily rhythms of hundreds of genes in microglia and astrocytes, brain cells responsible for immune response and communication between neurons. These disruptions could lead to accelerated disease progression and potentially be addressed through therapies targeting the circadian system.

Key Takeaways:

• Alzheimer's disease disrupts the circadian rhythms of brain cells involved in clearing amyloid plaques, leading to accelerated disease progression and sleep disturbances.
• The study found that amyloid accumulations in the brain throw off the daily rhythms of hundreds of genes in microglia and astrocytes, brain cells responsible for immune response and communication between neurons.
• The affected genes are generally involved in helping microglial cells break down waste material from the brain, including amyloid.
• Researchers discovered that the presence of amyloid creates new rhythms in hundreds of genes that do not typically have a circadian pattern of activity, hinting at the complexity of the disease's mechanisms.
• The findings suggest exploring therapies that target circadian cycles in microglia and astrocytes to support healthy brain function.
• Dr. Erik S. Musiek, a neurologist and expert in aging and dementia, emphasized the importance of addressing sleep disturbances, which are among the most frequent concerns reported by caregivers of Alzheimer's patients.
• The study was funded by the National Institute on Aging, the National Institute of Neurological Disorders and Stroke, and the National Institutes of Health.

Statistics:

• 82 genes are associated with Alzheimer's disease risk, with the circadian rhythm controlling the activity of about half of those (Sheehan et al., 2025).
• Hundreds of genes in microglia and astrocytes are affected by amyloid accumulations, disrupting their daily rhythms (Sheehan et al., 2025).
• 20% of all genes in the human genome are controlled by the circadian clock, managing processes such as digestion, the immune system, and the sleep-wake cycle (Musiek et al., 2025).
• Alzheimer's disease is characterized by accumulated amyloid protein in the brain, with known risk factors including age, genetics, and lifestyle (National Institute on Aging).
• The National Institutes of Health (NIH) provided funding for the study through grants R01AG054517, T32AG058518, and R00AG061231.

Sources:

• Sheehan PW, Fass S, Sapkota D, Kang S, Hollis HC, Lawrence JH, Anafi RC, Dougherty JD, Fryer JD, Musiek ES. A glial circadian gene expression atlas reveals cell type and disease-specific reprogramming in response to amyloid pathology or aging. Nature Neuroscience. October 23, 2025. DOI: 10.1038/s41593-025-02067-1.
• Original text from WashU Medicine: https://medicine.washu.edu/news/alzheimers-disrupts-circadian-rhythms-of-plaque-clearing-brain-cells/
• National Institute on Aging: Alzheimer's Disease Facts and Figures.
• National Institute of Neurological Disorders and Stroke: Alzheimer's Disease.