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

AIBL Research Group

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish
Article number47
Number of pages11
JournalTranslational Psychiatry
Volume8
Issue number1
DOIs
Publication statusPublished - 1 Dec 2018

Fingerprint

Aquaporin 4
Amyloid
Sleep
Brain
Aquaporins
Positron-Emission Tomography
Observational Studies
Single Nucleotide Polymorphism
Life Style
Cross-Sectional Studies
Biomarkers
Weights and Measures

Cite this

@article{0666ab827e5e44a3bcc744bc690074ce,
title = "Genetic variation in Aquaporin-4 moderates the relationship between sleep and brain Aβ-Amyloid burden",
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.",
author = "{AIBL Research Group} and Rainey-Smith, {Stephanie R.} and Mazzucchelli, {Gavin N.} and Villemagne, {Victor L.} and Brown, {Belinda M.} and Tenielle Porter and Michael Weinborn and Bucks, {Romola S.} and Lidija Milicic and Sohrabi, {Hamid R.} and Kevin Taddei and David Ames and Paul Maruff and Masters, {Colin L.} and Rowe, {Christopher C.} and Olivier Salvado and Martins, {Ralph N.} and Laws, {Simon M.}",
year = "2018",
month = "12",
day = "1",
doi = "10.1038/s41398-018-0094-x",
language = "English",
volume = "8",
journal = "Translational Psychiatry",
issn = "2158-3188",
publisher = "Nature Publishing Group",
number = "1",

}

Genetic variation in Aquaporin-4 moderates the relationship between sleep and brain Aβ-Amyloid burden. / AIBL Research Group.

In: Translational Psychiatry, Vol. 8, No. 1, 47, 01.12.2018.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Genetic variation in Aquaporin-4 moderates the relationship between sleep and brain Aβ-Amyloid burden

AU - AIBL Research Group

AU - Rainey-Smith, Stephanie R.

AU - Mazzucchelli, Gavin N.

AU - Villemagne, Victor L.

AU - Brown, Belinda M.

AU - Porter, Tenielle

AU - Weinborn, Michael

AU - Bucks, Romola S.

AU - Milicic, Lidija

AU - Sohrabi, Hamid R.

AU - Taddei, Kevin

AU - Ames, David

AU - Maruff, Paul

AU - Masters, Colin L.

AU - Rowe, Christopher C.

AU - Salvado, Olivier

AU - Martins, Ralph N.

AU - Laws, Simon M.

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85042667501&partnerID=8YFLogxK

U2 - 10.1038/s41398-018-0094-x

DO - 10.1038/s41398-018-0094-x

M3 - Article

VL - 8

JO - Translational Psychiatry

JF - Translational Psychiatry

SN - 2158-3188

IS - 1

M1 - 47

ER -