30 May Genetic variation in Aquaporin-4 moderates the relationship between sleep and brain Aβ-amyloid burden.
The Glymphatic dysfunction characterized by a failure of interstitial solute clearance is a central feature of natural brain aging, as well as Alzheimer’s disease and ischemic and hemorrhagic stroke. Researchers have suspected the glymphatic system to be a mechanism for amyloid β clearance, a known protein plaque found in the brain of Alzheimer’s disease sufferers. Damaging Aquaporin-4 (AQP4), a water-channel protein has been shown to cause build-up of Amyloid β in mice.
Genetic variation of Aquaporin-4 in humans and its affect on Amyloid burden and sleep is largely unknown.
This study was conducted on cognitively normal older adults. 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.
Certain variations were found to be associated with poorer sleep quality, while others affected sleep latency, duration and brain Aβ-amyloid burden.
These findings supports that the Glymphatic system plays a role in Amyloid β clearance and genetic variations may impair this function leading to plaque build-up.
Rainey-Smith SR, Mazzucchelli GN, Villemagne VL, et al. Genetic variation in Aquaporin-4 moderates the relationship between sleep and brain Aβ-amyloid burden. Translational Psychiatry. 2018;8:47. doi:10.1038/s41398-018-0094-x.
Plog BA, Nedergaard M. The glymphatic system in CNS health and disease: past, present and future. Annual review of pathology. 2018;13:379-394. doi:10.1146/annurev-pathol-051217-111018.