APP and Alzheimer disease: Although familial AD, or early-onset AD (EOAD), is caused by rare and highly penetrant mutations in 1 of 3 genes [amyloid precursor protein (APP), presenilin 1 (PSEN 1), and presenilin 2 (PSEN 2)], a majority (>90%) of AD cases are sporadic and classified as late-onset AD (LOAD).