Influence of an AQP4 haplotype and sleep duration on early Alzheimer's disease

INTRODUCTION: Aquaporin-4 (AQP4) is thought to facilitate Alzheimer's disease (AD) protein clearance during sleep. We examined whether AQP4 genetic variation was associated with AD pathology or modified the association between sleep duration and AD biomarkers. METHODS: A total of 450 dementia-free participants (mean age = 58 ± 9.9; women = 54%) from the Framingham Heart Study (FHS) with sleep duration measured by self-report and amyloid-β (Aβ) and tau burden quantified using positron emission tomography (PET) were analyzed. RESULTS: AQP4 was not associated with Aβ or tau burden in the overall sample. However, for participants aged less than 60, minor allele carriers displayed lower regional tau burden compared to homozygote majors. AQP4 modified the relationship between short sleep (≤6 hours) and medial temporal tau; short sleep duration was associated with higher medial temporal tau in minor allele carriers, while the opposite was observed in homozygote majors. DISCUSSION: AQP4 genetic variation may influence early tau accumulation and vulnerability to sleep-related AD pathology.