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Journal article
Exploring how genetic variation within Aquaporin‐4, influences the relationship between sleep and amyloid beta
Alzheimer's & dementia, Vol.20(Suppl. 1), e092408
2024
Abstract
Background
The glymphatic system has been suggested as an important clearance mechanism for amyloid‐β (Aβ) during sleep. Animal and cellular models have suggested this clearance mechanism involves the water‐channel protein, Aquaporin‐4 (encoded by the AQP4 gene), located primarily in the astrocytic end‐feet. We have previously reported on the interaction between genetic variants within AQP4, sleep and cross‐sectional cortical amyloid‐β (Aβ) burden. This study investigated how the relationship between AQP4 genetic variants and sleep may further influence changes in cortical Aβ levels.
Methods
The current study assessed cognitively unimpaired individuals enrolled in the Australian Imaging, Biomarker and Lifestyle (AIBL) Study of Ageing, who were considered Aβ accumulators (n = 319). Aβ accumulators were defined as those who had a high baseline level of cortical Aβ (centiloid ³20), or a positive rate of change in cortical Aβ, calculated using a minimum of 3 study time‐points. 13 AQP4 gene variants were selected for analysis based on fine mapping of the gene region, and sleep was assessed using measures calculated from the Pittsburgh Sleep Quality Index (PSQI) questionnaire. The relationship between AQP4 gene variants and rate of Aβ accumulation was investigated using linear regressions. Additional linear regression models with AQP4 variant x sleep measure interaction terms and post‐hoc simple slopes were analysed to assess how these relationships may influence Aβ accumulation.
Results
AQP4‐rs68006382 was associated with Aβ accumulation, where minor allele carriers/homozygotes were observed to have a higher rate of accumulation when compared to major allele homozygotes. Linear regressions with AQP4 variant x sleep measure interaction terms revealed that in AQP4‐rs68006382 minor allele carriers there was a significant relationship between Aβ accumulation and sleep quality. Additionally, interaction analysis revealed a relationship between Aβ accumulation and sleep latency in AQP4‐rs3875089 minor allele carriers.
Conclusion
The results of this study confirm our previous findings and suggests that interactions between AQP4 genotypes and sleep measures are also associated with the rate of Aβ accumulation.
Details
- Title
- Exploring how genetic variation within Aquaporin‐4, influences the relationship between sleep and amyloid beta
- Authors/Creators
- Tenielle Porter - Curtin UniversityAyeisha Milligan Armstrong - Curtin UniversityVincent Dore - Australian e-Health Research CentreEleanor K. O’Brien - Edith Cowan UniversityPierrick Bourgeat - Commonwealth Scientific and Industrial Research OrganisationPaul Maruff - Australian e-Health Research CentreChristopher C. Rowe - Austin HealthStephanie Rainey Smith - Murdoch University, Centre for Healthy AgeingVictor L Villemagne - University of PittsburghSimon M. Laws - Edith Cowan UniversityThe AIBL Research Group
- Publication Details
- Alzheimer's & dementia, Vol.20(Suppl. 1), e092408
- Publisher
- Wiley Periodicals LLC on behalf of Alzheimer's Association.
- Number of pages
- 2
- Identifiers
- 991005732484007891
- Copyright
- © 2024 The Alzheimer's Association.
- Murdoch Affiliation
- Murdoch University; Centre for Healthy Ageing
- Language
- English
- Resource Type
- Journal article
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