Journal article
Genetic variation in Aquaporin-4 moderates the relationship between sleep and brain Aβ-amyloid burden
Translational Psychiatry, Vol.8, Article number: 47
2018
Abstract
The glymphatic system is postulated to be a mechanism of brain Aβ-amyloid clearance and to be most effective during sleep. Ablation of the astrocytic end-feet expressed water-channel protein, Aquaporin-4, in mice, results in impairment of this clearance mechanism and increased brain Aβ-amyloid deposition, suggesting that Aquaporin-4 plays a pivotal role in glymphatic function. Currently there is a paucity of literature regarding the impact of AQP4 genetic variation on sleep, brain Aβ-amyloid burden and their relationship to each other in humans. To address this a cross-sectional observational study was undertaken in cognitively normal older adults from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study. Genetic variants in AQP4 were investigated with respect to self-reported Pittsburgh Sleep Quality Index sleep parameters, positron emission tomography derived brain Aβ-amyloid burden and whether these genetic variants moderated the sleep-Aβ-amyloid burden relationship. One AQP4 variant, rs72878776, was associated with poorer overall sleep quality, while several SNPs moderated the effect of sleep latency (rs491148, rs9951307, rs7135406, rs3875089, rs151246) and duration (rs72878776, rs491148 and rs2339214) on brain Aβ-amyloid burden. This study suggests that AQP4 genetic variation moderates the relationship between sleep and brain Aβ-amyloid burden, which adds weight to the proposed glymphatic system being a potential Aβ-amyloid clearance mechanism and suggests that AQP4 genetic variation may impair this function. Further, AQP4 genetic variation should be considered when interpreting sleep-Aβ relationships.
Details
- Title
- Genetic variation in Aquaporin-4 moderates the relationship between sleep and brain Aβ-amyloid burden
- Authors/Creators
- S.R. Rainey-Smith (Author/Creator) - Edith Cowan UniversityG.N. Mazzucchelli (Author/Creator) - Edith Cowan UniversityV.L. Villemagne (Author/Creator) - Florey Institute of Neuroscience and Mental HealthB.M. Brown (Author/Creator) - Edith Cowan UniversityT. Porter (Author/Creator)M. Weinborn (Author/Creator) - The University of Western AustraliaR.S. Bucks (Author/Creator) - The University of Western AustraliaL. Milicic (Author/Creator) - Cooperative Research Centre for Mental HealthH.R. Sohrabi (Author/Creator) - Edith Cowan UniversityK. Taddei (Author/Creator) - Edith Cowan UniversityD. Ames (Author/Creator) - St Vincent's HealthP. Maruff (Author/Creator) - Florey Institute of Neuroscience and Mental HealthC.L. Masters (Author/Creator) - Florey Institute of Neuroscience and Mental HealthC.C. Rowe (Author/Creator) - Austin HealthO. Salvado (Author/Creator) - CSIRO Health and Biosecurity/Australian e-Health Research Centre, Herston, AustraliaR.N. Martins (Author/Creator) - Edith Cowan UniversityS.M. Laws (Author/Creator) - Edith Cowan University
- Publication Details
- Translational Psychiatry, Vol.8, Article number: 47
- Publisher
- Macmillan Publishers Limited
- Identifiers
- 991005542722007891
- Murdoch Affiliation
- School of Psychology and Exercise Science
- Language
- English
- Resource Type
- Journal article
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