APP and early-onset autosomal dominant Alzheimer disease: The amyloid precursor protein (APP), initially described in 1987,1–3 is the precursor to the amyloid-beta (Aβ) peptide that deposits in the brain of individuals with Alzheimer’s disease (AD).4 In mammals, it has two homologous proteins, APLP1 and APLP2, that possess a similar structure but do not contain the Aβ domain.