APP and familial Alzheimer disease: APP is a ubiquitously expressed type I transmembrane protein and of central importance in Alzheimer’s disease for the following reasons: (1) inherited mutations in APP cause a dominant, early-onset form of familial Alzheimer’s disease (FAD) with full penetrance (8), (2) APP locus duplication is sufficient to inherit Alzheimer’s disease (9, 10, 11); and (3) genome-wide association studies (GWAS) revealed APP gene variants (single nucleotide polymorphisms) that associate with an increased Alzheimer’s disease risk (12, 13, 14).