Polygenic risk for Alzheimer's disease influences precuneal volume in two independent general populations

Alzheimer's disease (AD) is heritable with complex genetic underpinnings. Based on previous results from large-scale genome-wide association studies, recent studies found an association between the polygenic risk score (PGRS) of AD and the structure of some preselected brain regions, but the effects of AD PGRS on all voxels of the brain have not been fully investigated. In the present study, we examined the voxel-wise effect of AD PGRS on the entire brain and the influence of AD PGRS on cognitive function in 2 independent healthy young cohorts. In both cohorts, an elevated AD PGRS was associated with a smaller precuneal volume, and the effect remained after excluding the APOE genotype. No correlation was found between AD PGRS and any cognitive measure in either sample. Finding a negative correlation between the AD PGRS and the precuneal volume could help to elucidate the mechanism of the genetic risk for AD and could provide a potential biomarker for early detection and possible interventions in AD.