APP and Alzheimer disease: While most AD cases are sporadic, less than 5% of the cases are caused by mutations in the amyloid precursor protein (APP) gene or presenilin 1 or 2 genes, leading to excessive production and accumulation of amyloid-β peptide (Aβ; Citron et al., 1992; Hendriks et al., 1992; Mullan et al., 1992; Suzuki et al., 1994; Harvey et al., 2003; Goate, 2006).