The study, conducted by ECU’s Centre for Precision Health (CPH), examined the aquaporin-4 (AQP4) gene. This gene helps control the movement of fluid through the brain, a function that supports the organ’s natural waste-clearing system.

The Brain’s Overnight Waste Removal System

The brain’s waste-removal process becomes especially active during sleep. Scientists believe it helps clear potentially harmful proteins, including proteins associated with Alzheimer’s disease.

Researchers found that the effects of sleep appeared to vary depending on which version of the AQP4 gene a person carried.

“Our study shows that individuals carrying certain AQP4 variants showed faster grey 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.”

Grey matter contains many of the brain cells involved in memory, decision-making, movement, and other essential functions. A decline in grey matter volume can be a sign of structural changes in the brain.

Sleep Effects Differed by Genetic Variant

The researchers analyzed 13 common AQP4 gene variants, along with participants’ self-reported sleep patterns, brain scans, and cognitive test results.

Among some participants, sleeping for fewer hours was associated with a faster decline in grey matter. In others, taking longer to fall asleep was linked to structural brain changes involving lower brain volume.

Cognitive performance also changed differently over time among people who experienced sleep disturbances. Whether the effect appeared beneficial or harmful depended on the specific AQP4 variant each 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.”

Toward Personalized Alzheimer’s Prevention

The findings suggest that two people with similar overall Alzheimer’s risk may not respond to poor sleep in the same way. Genetic differences could help explain why brain decline progresses more quickly in some individuals than in others.

The researchers recommended conducting clinical trials that incorporate genetic information. Such studies could test whether improving sleep habits can reduce inherited vulnerability and change long-term brain outcomes associated with 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.”

The study, “Evidence for Direct and Sleep-Moderated Relationships between Aquaporin -4 Genetic Variants and Alzheimer’s Disease Phenotypes” is published online in Alzheimer’s & Dementia, the Journal of the Alzheimer’s Association.