Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/17800
Title: Genetic variation in Aquaporin-4 moderates the relationship between sleep and brain Aβ-amyloid burden.
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
Affiliation: Centre of Excellence for Alzheimer's Disease Research and Care, School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia
Sir James McCusker Alzheimer's Disease Research Unit, Hollywood Private Hospital, Perth, WA, Australia
Collaborative Genomics Group, Centre of Excellence for Alzheimer's Disease Research and Care, School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia
Department of Nuclear Medicine & Centre for PET, Austin Health, Heidelberg, Victoria, Australia
School of Psychology and Exercise Science, Murdoch University, Murdoch, WA, Australia
Co-operative Research Centre for Mental Health, Carlton, VIC, Australia
School of Psychological Science, University of Western Australia, Crawley, WA, Australia
Department of Biomedical Sciences, Macquarie University, North Ryde, NSW, Australia
Academic Unit for Psychiatry of Old Age, St. Vincent's Health, The University of Melbourne, Kew, VIC, Australia
National Ageing Research Institute, Parkville, VIC, Australia
CogState Ltd., Melbourne, VIC, Australia
CSIRO Health and Biosecurity/Australian e-Health Research Centre, Herston, QLD, Australia..
School of Biomedical Sciences, Faculty of Health Sciences, Curtin Health Innovation Research Institute, Curtin University, Bentley, WA, Australia
Issue Date: 26-Feb-2018
EDate: 2018-02-26
Citation: Translational psychiatry 2018; 8(1): 47
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.
URI: http://ahro.austin.org.au/austinjspui/handle/1/17800
DOI: 10.1038/s41398-018-0094-x
ORCID: 0000-0001-5819-3026
0000-0001-8017-8682
0000-0002-4355-7082
0000-0003-3910-2453
PubMed URL: 29479071
Type: Journal Article
Review
Appears in Collections:Journal articles

Files in This Item:
There are no files associated with this item.


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.