The relationship between genetic variation in Aquaporin-4, sleep quality measures and Alzheimer’s disease-related phenotypes.

Genetic variants within the Aquaporin-4 gene ( AQP4 ) have been associated with Alzheimer’s disease (AD) diagnosis, rate of cognitive decline, and brain amyloid-β (Aβ) burden. Additionally, AQP4 variants have been reported to moderate the relationship between sleep and brain Aβ burden. As yet, the impact of interactions between AQP4 variants and sleep on other AD-related phenotypes, and measures of disease progression, remains largely unexplored. The current study sought to assess relationships between AQP4 variants, self-reported sleep measures, and AD-related phenotypes, including cognition, brain Aβ burden, and brain volumetrics, in a cohort of cognitively unimpaired individuals at an increased risk of AD due to brain Aβ accumulation. Analyses used data from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study. When assessing the relationship between AQP4 variants and sleep components, several associations were observed. Specifically, AQP4 variants were both directly, and in interaction with sleep latency and overall quality, associated with cross-sectional and longitudinal Aβ burden, however these associations did not survive correction for multiple testing. When assessing effects on cognition, A QP4 variants were associated directly, as well as in interaction with sleep disturbances and duration, with several cognitive domains both cross-sectionally and longitudinally. Finally, A QP4 variants were associated directly, and in interaction with sleep duration, latency and overall quality, with regional brain volumes, both cross-sectionally and longitudinally. The findings from this study provide further evidence for the relationship between AQP4 genetic variation and AD-related phenotypes, as well as for the interaction between sleep and these genetic variants.