APP and familial Alzheimer disease: Mutations in APP on chromosome 21q (Levy et al., 1990; Goate et al., 1991; Tanzi and Bertram, 2005; Bertram et al., 2010) and in PS 1 and 2 genes (PSEN1 and PSEN2, respectively) on chromosomes 14 and 1 (Levy-Lahad et al., 1995; Rogaev et al., 1995; Sherrington et al., 1995) can cause early-onset familial Alzheimer’s disease (FAD), characterized by an increased Aβ42/Aβ40 ratio biochemically.