Observational studyTranslational psychiatry2018
Genetic variation in Aquaporin-4 moderates the relationship between sleep and brain Aβ-amyloid burden.
Observational study in Translational psychiatry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06857136 (The Role of the Glymphatic System Avaluated Thourgh mr Imaging in the Diagnosis and Management of NPH), which is not on this map. Cited by 90 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
The Role of the Glymphatic System Avaluated Thourgh mr Imaging in the Diagnosis and Management of NPH
Who cites it
90 citing papers in PubMed, 2 syntheses or guidelines pooled it, 140 citations in OpenAlex.
- Sleep Quality and Aging: A Systematic Review on Healthy Older People, Mild Cognitive Impairment and Alzheimer's Disease.International journal of environmental research and public health · 2022Pooled it
- Pooled it
- Outdoor Air Pollution, Perivascular Space Morphology, and Cognition in Preadolescence.Biological psychiatry global open science · 2026Article
- Single-cell multiomics connects 3D genome and transcriptome alterations in Alzheimer's disease.Science (New York, N.Y.) · 2026Article
- Evidence for direct and sleep-moderated relationships between aquaporin-4 genetic variants and Alzheimer's disease phenotypes.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Influence of an AQP4 haplotype and sleep duration on early Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Genetic Architecture of Perivascular Space Morphology in the Pediatric Brain.bioRxiv : the preprint server for biology · 2026Article
- Genetic variation in the glymphatic pathway predicts cognition and neurodegeneration in preclinical Alzheimer's disease.Research square · 2026Article
- Canine Cognitive Dysfunction and Alzheimer's Disease: Pathophysiological Relationships and the Impact of Glymphatic System Impairment on Neurodegeneration.Veterinary sciences · 2026Review
- Sleep disturbances and Alzheimer's disease: a multiscale approach from exposome to neurobiology and precision medicine.GeroScience · 2026Review
- The Prevalence of Sleep Disorders in Populations with Glymphatic Dysfunction: A Systematic Review and Meta-Analysis.Biology · 2026Review
- Targeting glymphatic-associated pathways for Alzheimer's disease: a review of non-invasive modulation strategies, mechanisms, and emerging evidence.Frontiers in immunology · 2026Review
- Sleep Abnormalities and Risk of Alzheimer's Disease.Current neurology and neuroscience reports · 2025Review
- Melatonin Mitigates Sleep Restriction-Induced Cognitive and Glymphatic Dysfunction Via Aquaporin-4 Polarization.Molecular neurobiology · 2025Article
- The Therapeutic Potential of Glymphatic System Activity to Reduce the Pathogenic Accumulation of Cytotoxic Proteins in Alzheimer's Disease.International journal of molecular sciences · 2025Review
- Sleep and Risk of Multiple Sclerosis: Bridging the Gap Between Inflammation and Neurodegeneration via Glymphatic Failure.Brain sciences · 2025Review
- Stress-Induced Sleep Dysregulation: The Roles of Astrocytes and Microglia in Neurodegenerative and Psychiatric Disorders.Biomedicines · 2025Review
- Association Between Single Nucleotide Polymorphisms in the Aquaporin-4 Gene and Longitudinal Changes in White Matter Free Water and Cognitive Function in Non-Demented Older Adults.Human brain mapping · 2025Article
- Insufficient Sleep and Alzheimer's Disease: Potential Approach for Therapeutic Treatment Methods.Brain sciences · 2024Review
- From Fundamentals to Innovation in Alzheimer's Disease: Molecular Findings and Revolutionary Therapies.International journal of molecular sciences · 2024Review
30 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.