New research suggests our genes and sleep habits work together to influence early brain and cognitive changes associated with Alzheimer’s disease, long before symptoms appear.
The study, published in Alzheimer’s and Dementia, 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.
The researchers 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 grey matter, while others—who reported taking longer to fall asleep—showed changes in brain structure associated with reduced brain volume.
“Our study shows it’s not just which genes you carry—it’s how those genes interact with the world around you,” said Ayeisha Milligan Armstrong, study author and postdoctoral research fellow at Edith Cowan University (ECU). “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 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.
“This moves us closer to understanding why some people decline faster than others, even when they have similar risk on paper,” said Simon Laws, Director of ECU's Centre for Precision Health. "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."
Next, the findings need replication in larger and more diverse cohorts. The authors recommend 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.
Data from Edith Cowan University