Leonenko G, Shoai M, Bellou E, et al. - In view of the fact that Alzheimer disease (AD) is the most common form of dementia among elderly people and is a major health problem worldwide, researchers tested the predictive accuracy for AD, mild cognitive impairment (MCI), and risk of amyloid deposition with polygenic risk score (PRS), including and excluding APOE genotypes in a large publicly available dataset with extensive phenotypic data (the Alzheimer's Disease Neuroimaging Initiative cohort). The authors discovered both APOE genotype and PRS predict AD and MCI. Only APOE predicts the deposition of amyloid. PRS, over and above APOE, predicts further progression to AD of people with MCI and amyloid-positive status. Even when genes in the APOE region were removed, the protein–lipid complex has the strongest connection with AD and amyloid deposition in pathway-specific PRS analyses.