Using explainable AI, genetics and neuroimaging to target the glymphatic system
The glymphatic system is a brain-wide perivascular clearance pathway which facilitates the clearance of Amyloid-beta, a pathological hallmark of Alzheimer’s disease, from the brain. It is regulated by the sleep-wake cycle. The function of the glymphatic system relies highly on the water channel aquaporin 4 (AQP4), which is expressed by the AQP4 gene. Identifying genetic variants of risk with respect to the function of the glymphatic system and the role of sleep on its function, and defining genetically stratified groups to identify suitable candidates for future studies will aid in the investigation of a link between sleep and neurodegeneration. However, the effects of single genetic variants are typically very small. Additionally the interaction between genes or single nucleotide polymorphisms (SNPs), as well as gene-environment interactions might impede the declaration of single genetic variants as statistically significant.