APP and familial Alzheimer disease: Although the vast majority of AD occur on a sporadic basis, mutations in three genes [amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2)] could lead to rare familial AD (FAD; <0.5%), whose symptoms occur earlier than sporadic AD, usually between 30 and 50 years of age, also named as early-onset AD.