Neurodegeneration - A Brick Wall for Population Aging: Multiple Genetic Interactions Predict Risk for Alzheimer’s Disease

Elizabeth Corder, Duke University
Rong Huang, Medical College of Georgia
Shirley Poduslo

Neurodegeneration is a brickwall to population aging. Alzheimer's brain pathology is almost universal, emerging in middle age and often symptomatic among the elderly. Individuals vary in the rate that changes accumulate, which has genetic determinants, e.g. APOE genotype. We investigated 180 patients and 120 spouse control subjects. A latent classification statistical model, i.e. GoM, identified five risk groups from information on age, sex, disease status, and multilocus genotypes (APOE, APOE promoter, APOCI, LDLr, cystatinC, cathepsinD). Onset age varied for three high-risk sets: 1) CST3:GA and CTSD:CT (<70 years) with permissive APOE promoters; 2)APOE44 and LDLr8:GG and LDLr13:TT (<75 years); 3)APOE34 and LDLr13:TC (<80 years). The absence of these combinations defined low-risk. APOE e23, e33 or e34 with receptor and promoter heterozygosity predicted long-life without dementia. These results indicate an approach to identification of determinants for AD and other brickwall neurodegenerative conditions.