New Delhi: A new study has found that a gene involved in the brain’s natural overnight cleaning process may influence how poor sleep affects brain changes associated with Alzheimer’s disease. Researchers say the findings could pave the way for more personalised strategies to reduce Alzheimer’s risk by considering both an individual’s genetic profile and sleep habits.

The research, conducted by the Centre for Precision Health at Edith Cowan University (ECU), examined variations in the aquaporin-4 (AQP4) gene and found that different genetic variants may alter how sleep quality affects brain structure and cognitive function.

Brain’s cleaning system becomes active during sleep

The AQP4 gene plays a key role in regulating the movement of fluid through the brain and supports the brain’s waste-removal system, often referred to as the glymphatic system.

Scientists believe this system becomes most active during sleep, helping clear waste products and potentially harmful proteins that have been linked to Alzheimer’s disease.

Efficient removal of these proteins is considered important for maintaining long-term brain health and may reduce the accumulation of substances associated with neurodegenerative disorders.

Gene variants influence sleep’s impact

The researchers analysed 13 common variants of the AQP4 gene alongside participants’ self-reported sleep patterns, brain scans and cognitive assessments.

The study found that the effects of poor sleep differed depending on which version of the AQP4 gene a person carried.

Among some participants, shorter sleep duration was associated with a faster decline in grey matter, while others experienced structural brain changes linked to reduced brain volume when they took longer to fall asleep.

Grey matter contains many of the brain cells responsible for memory, reasoning, movement and other essential functions. A reduction in grey matter volume is considered an indicator of structural changes within the brain.

Cognitive changes varied among participants

Researchers also observed differences in cognitive performance over time among people experiencing sleep disturbances.

The impact of poor sleep appeared to be either beneficial or harmful depending on the specific AQP4 genetic variant carried by an individual.

According to the researchers, the findings suggest that genetics may partly explain why some people experience faster brain decline than others despite having similar overall Alzheimer’s risk factors.

The study indicates that sleep is not equally protective—or equally harmful—for everyone.

Personalised prevention may be possible

The researchers believe the findings support the development of more personalised approaches to Alzheimer’s prevention.

Rather than applying identical recommendations to everyone at risk, future prevention strategies may take both genetic background and lifestyle factors such as sleep quality into account.

However, the researchers cautioned that the findings are preliminary and require confirmation through larger and more diverse studies before they can influence clinical practice.

They also stressed that the results do not justify routine genetic testing for the AQP4 gene at this stage.

More research needed

The research team recommended future clinical trials incorporating genetic information to determine whether improving sleep habits can reduce inherited vulnerability to Alzheimer’s disease.

Such studies could help establish whether targeted sleep interventions are more effective for people with specific genetic profiles.

The researchers said this precision-health approach may eventually enable doctors to identify individuals who are most likely to benefit from particular lifestyle interventions instead of adopting a one-size-fits-all strategy.

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

While the findings add to growing evidence linking sleep and brain health, experts emphasise that maintaining healthy sleep habits remains beneficial for overall wellbeing regardless of genetic background.