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A disrupted sleep cycle may do more than cause restless nights for Alzheimer’s patients—it might actually drive the disease itself. A new study from Washington University School of Medicine reveals that Alzheimer’s interferes with the brain’s circadian rhythm, throwing hundreds of genes out of sync. This internal timing breakdown could accelerate amyloid buildup and brain decline.

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When the Brain’s Clock Falters

People living with Alzheimer’s often experience disturbed sleep, daytime drowsiness, and confusion at certain times of day, particularly during “sundowning.” These symptoms point to a malfunctioning circadian system—the body’s internal clock that governs sleep, wakefulness, and many vital biological processes.

The study, published in Nature Neuroscience, shows that Alzheimer’s disrupts normal gene activity in microglia and astrocytes, two types of brain cells responsible for maintaining healthy neurons and clearing waste. “About half of the genes linked to Alzheimer’s are controlled by the body’s internal clock,” said Dr. Erik S. Musiek, senior author of the study. “When these rhythms break, so does the brain’s balance.”

Amyloid Plaques Scramble Gene Rhythms

To explore how deeply Alzheimer’s disturbs the brain’s timing, researchers studied mice genetically engineered to develop amyloid plaques. By analyzing brain samples taken every two hours over a full day, the team discovered that amyloid buildup disrupted the regular on-off rhythm of hundreds of genes in microglia and astrocytes.

Normally, these genes help the brain clear out toxins like amyloid. But when their activity became erratic, that cleanup system weakened—leading to more plaque accumulation and inflammation. Surprisingly, the disease also created new, abnormal rhythms in genes tied to stress and immune responses, suggesting the brain was trying to adapt to the chaos.

Restoring the Rhythm Could Slow Disease Progression

The findings open the door to therapies aimed at resetting or strengthening the brain’s circadian clock. By restoring regular gene activity, scientists hope to protect the brain from amyloid damage and slow memory loss.

“Manipulating the circadian system in specific cell types could help us prevent or delay Alzheimer’s,” Musiek said. “Understanding how the brain’s clock fails gives us a powerful new way to target the disease.”