HMN 2026: How How sleep and AQP4 gene variants may jointly shape early Alzheimer’s brain changes

New research from Edith Cowan University has discovered an important link between genes and sleep habits, suggesting they work together to influence early brain and cognitive changes associated with Alzheimer’s disease long before symptoms appear. The study is published in the journal Alzheimer’s & Dementia.

The study by Edith Cowan University’s Center for Precision Health (CPH) focused on the aquaporin-4 (AQP4) gene, which helps regulate the movement of fluid through the brain.

This process supports the brain’s built-in waste removal system, which is most active overnight and is thought to help clear proteins linked to Alzheimer’s disease.

“Our study shows that individuals carrying certain AQP4 variants showed faster gray matter loss when they reported shorter sleep,” researcher Dr. Ayeisha Milligan Armstrong said.

“It’s not just which genes you carry—it’s how those genes interact with the world around you. The same variant can look protective or detrimental depending on how someone is sleeping. That’s important, because sleep is one of the few modifiable factors people can actually act on.”

The team examined 13 common variants of the AQP4 gene, self-reported sleep patterns, brain scans and cognitive performance.

For some participants, shorter sleep duration was linked with faster loss of gray matter, while others who reported taking longer to fall asleep showed changes in brain structure associated with reduced brain volume.

The study also found that patterns of cognitive performance over time differed in people experiencing sleep disturbances, with the direction of the effect depending on which AQP4 variant a person carried.

“We’ve known for a while that poor sleep and Alzheimer’s risk are linked,” researcher Dr. Tenielle Porter said.

“What this shows is that rather than assuming everyone at risk follows the same pathway, a more targeted and personalized approach to Alzheimer’s prevention may be needed. But we’re not at the point of recommending genetic testing; our findings need replication in larger and more diverse cohorts.”

The study recommended genetics-informed clinical trials to determine whether changing sleep patterns can offset genetic risk and alter long-term brain outcomes related to Alzheimer’s disease.

“This moves us closer to understanding why some people decline faster than others, even when they have similar risk on paper,” CPH Director Professor Simon Laws said.

“Identifying who is most vulnerable, and who is most likely to benefit from a particular lifestyle intervention, is where precision health needs to go rather than treating everyone at risk of Alzheimer’s the same way.”

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