Alzheimer’s Disease‐Related Polygenic Risk Score Profiles and Brain Proteinopathies

Genome‐wide association studies (GWAS) have identified more than 70 genetic loci significantly associated with Alzheimer’s disease (AD). AD‐associated genetic variants have been mapped to biological pathways including endocytosis, oxidative stress, immune response, synaptic plasticity, lipid metabolic, apoptotic process, and amyloid‐beta formation. These diverse biological pathways may be differentially responsible for brain pathologies and combinations of proteinopathies. Pathway‐specific polygenic risk scores (PRSs) are useful to estimate an individual’s genetic liability according to well‐characterized biologic pathways. In this study, we investigated differences in AD‐PRSs calculated by biological pathways in different brain proteinopathies.