Author Identifier (ORCID)
Tenielle Porter’s ORCID record 
Ayeisha Milligan Armstrong’s ORCID record
Eleanor O'Brien’s ORCID record
Mitchell Turner’s ORCID record
Belinda M. Brown’s ORCID record 
Victor L. Villemagne’s ORCID record
Abstract
Introduction: Variants in the aquaporin-4 gene (AQP4) have been associated with Alzheimer's disease (AD) diagnosis, cognition, and brain amyloid beta (Aβ) and may affect the sleep and Aβ relationship. Their association with other AD-related phenotypes/disease progression remain largely unknown. Methods: Associations between AQP4 variants, self-reported sleep measures, and AD-related phenotypes in cognitively unimpaired individuals with evidence of Aβ accumulation were examined using data from the Australian Imaging, Biomarkers and Lifestyle study. Results: AQP4 variants were directly associated with regional brain volumes, atrophy, and cognition. They were also associated with differences in regional brain volumes and atrophy in interaction with sleep duration, latency, and quality. Finally, AQP4 variants were associated with cognitive decline in interaction with sleep disturbances. Discussion: These findings support a relationship between AQP4 and AD phenotypes, both directly and through their interaction with sleep.
Keywords
amyloid beta, aquaporin-4 (AQP4), brain volume, cognition, glymphatic system, sleep
Document Type
Journal Article
Date of Publication
6-1-2026
Article Number
e71516
ISSN
15525260
Volume
22
Issue
6
PubMed ID
42216479
Publication Title
Alzheimer's & Dementia
Publisher
Wiley
School
Centre for Precision Health / School of Medical and Health Sciences
RAS ID
99966
Funding Information
The study received partial financial support from the Alzheimer's Association (USA), the Alzheimer's Drug Discovery Foundation, an anonymous foundation, the Science and Industry Endowment Fund, the Dementia Collaborative Research Centers, the Victorian Government's Operational Infrastructure Support program, the Australian Alzheimer's Research Foundation (now Alzheimer's Research Australia), the National Health and Medical Research Council (NHMRC), and the Yulgilbar Foundation.
Funding received from the National Health and Medical Research Council (NHMRC)
GNT1161706, GNT2001320, GNT1197315
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Recommended Citation
Porter, T., Armstrong, A. M., O’Brien, E. K., Doré, V., Bourgeat, P., Turner, M., Maruff, P., Rowe, C. C., Brown, B. M., Villemagne, V. L., Rainey‐Smith, S. R., & Laws, S. M. (2026). Evidence for direct and sleep‐moderated relationships between aquaporin‐4 genetic variants and Alzheimer’s disease phenotypes. Alzheimer’s & Dementia, 22(6), Article e71516. https://doi.org/10.1002/alz.71516