Membership in Genetic Groups Predicts Alzheimer Disease

The multiple polymorphisms contributing to Alzheimer disease (AD) have been difficult to identify. Three essentially sufficient risk sets were found using a fuzzy latent classification statistical model; that is, grade-of-membership analysis, and genotypes for APOE, APOCI, LDLr, cystatin C, and cathepsin D (180 cases, 120 controls). These were: (a) CST3:G (A) under bar and CTSD:C (T) under bar (b) APOE <(44)under bar > and LDLr8:<(GG)under bar > and LDLr13:<(TT)under bar >; and (c) APOE3 (4) under bar and LDLr13:(T) under barC. Consonance with one of the groups and high aggregate membership carried > 800-fold elevated risk for AD. The absence of these combinations defined low risk. APOE3/- with heterozygous promoter and receptor genotypes predicted long life without dementia.