Pathway-Specific Genetic Risk Scores for Alzheimer’s Disease to Differentiate Regional Cortical Atrophy in Older Adults

Brain aging is highly variable and represents a challenge to delimit aging from disease processes. Moreover, genetic variation may influence both aging and disease. Here we used a genetic risk score (GRS) based on twenty loci previously identified to be associated with late-onset Alzheimer’s disease (AD) at genome-wide significance and evaluated the polygenic effects on cortical thickness (CT) of older adults from a population cohort (1000BRAINS). The aim was to develop a genetically informed predictor that helps to differentiate disease-associated from aging-associated regional atrophy in the cerebral cortex. The presented data reflect the allelic scoring information to calculate six pathway-specific GRS (cholesterol metabolism, APP metabolism, MAPT metabolism, cytoskeleton/axon development, immune response, endocytosis), and a total GRS (total) that summarizes the effects across all pathways.