APP and Alzheimer disease: Initial insights into the pathogenesis of AD came from genetic studies of familial autosomal dominant AD cases that identified full penetrant single-pathogenic mutations in genes regulating the production of the Aβ peptide, including the amyloid precursor protein gene (APP) as well as in those genes encoding the γ-secretase subunits, presenilin 1 and 2 (PSEN1, PSEN2).