APP and Alzheimer disease: Though some cases are caused by highly penetrant mutations in amyloid precursor protein (APP) or the presenilins (PSEN1 and PSEN2), components of the enzymatic secretase complex that processes APP to the beta-amyloid peptide, most AD cases are “sporadic” (Alzheimer’s Disease Collaborative 1995; Goate et al. 1991; Lendon et al. 1997; Levy-Lahad et al. 1995; Rogaev et al. 1995).