Genetic variation in Aquaporin-4 moderates the relationship between sleep and brain Aβ-amyloid burden

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 depos...

Full description

Saved in:
Bibliographic Details
Published in:Translational psychiatry 2018-02, Vol.8 (1), p.47-11, Article 47
Main Authors: Rainey-Smith, Stephanie R, Mazzucchelli, Gavin N, Villemagne, Victor L, Brown, Belinda M, Porter, Tenielle, Weinborn, Michael, Bucks, Romola S, Milicic, Lidija, Sohrabi, Hamid R, Taddei, Kevin, Ames, David, Maruff, Paul, Masters, Colin L, Rowe, Christopher C, Salvado, Olivier, Martins, Ralph N, Laws, Simon M
Format: Article
Language:English
Subjects:
Aged
Aged, 80 and over
Amyloid beta-Peptides - metabolism
Aquaporin 4 - genetics
Aquaporins
Australia
Brain - diagnostic imaging
Brain - metabolism
Cross-Sectional Studies
Female
Humans
Male
Polymorphism, Single Nucleotide
Positron-Emission Tomography
Sleep
Sleep - physiology
Sleep Wake Disorders - physiopathology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2158-3188
2158-3188
DOI:10.1038/s41398-018-0094-x