Research led by Edith Cowan University in Australia suggests the impact of genetic mutations that impact Alzheimer’s disease risk are influenced by a person’s sleep habits.
As reported in the journal Alzheimer’s & Dementia, the researchers confirmed links with aquaporin-4 gene (AQP4) variants and changes in brain volume, atrophy and cognition linked to Alzheimer’s disease.
The investigators also showed how long people sleep, how long it takes them to fall asleep, how often their sleep is disturbed, and how good or poor their sleep is overall contributed to the effect of these mutations.
“Our study shows that individuals carrying certain AQP4 variants showed faster grey matter loss when they reported shorter sleep,” said study co-author Ayeisha Milligan Armstrong, PhD, a researcher at Edith Cowan University, in a press statement.
“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.”
Researchers now think the brain gets rid of amyloid‑beta using a kind of plumbing system that washes waste away along the outside of blood vessels. In this system, fluid moves through the spaces around blood vessels, helped by tiny water channels called aquaporin‑4, encoded by AQP4, which sit on the parts of astrocyte cells that wrap tightly around those vessels.
“Given that AQP4 has been identified as an important mediator of brain amyloid beta clearance, variation within the AQP4 gene has been investigated in relation to neurodegenerative diseases and their associated phenotypes,” write the authors.
“A bi-directional relationship has been observed between suboptimal sleep and increasing brain amyloid beta accumulation…Importantly, a previous study utilizing data from the Australian Imaging, Biomarker and Lifestyle cohort reported that the relationship between sleep and cross-sectional brain amyloid beta burden was moderated by genetic variants in AQP4.”
To investigate this link further, the researchers studied 351 cognitively normal people already showing ongoing build‑up of brain amyloid‑beta on positron emission tomography (PET) imaging. They genotyped the group for 13 mutations in the AQP4 gene and also assessed sleep duration and quality, brain volume, amyloid burden and cognition scores.
Several AQP4 variants interacted with sleep measures to predict gray‑matter atrophy, brain ventricular volume, white‑matter volume, and cognitive decline. For example, people carrying certain variants who also had shorter sleep duration were more likely to have faster grey‑matter loss, and other variants magnified the impact of poorer global sleep quality on ventricular enlargement in the brain.
One variant showed a direct association with better global cognitive performance and two other variants seemed to be linked to less cognitive decline as sleep disturbances increased.
“We’ve known for a while that poor sleep and Alzheimer’s risk are linked,” said first author Tenielle Porter, PhD, also a researcher at Edith Cowan University.
“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.”
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