APP and Alzheimer disease: Support for this hypothesis came from autosomal‐dominant familial AD cases, which ultimately originate from aberrant Aβ production and aggregation due to APP, PSEN1, or PSEN2 gene mutations (Sherrington et al. 1995; Levy‐Lahad et al. 1995; Tomiyama et al. 2008) or due to defects in Aβ clearance as a result of the presence of the APOE4 allele in late‐onset AD (Holtzman et al. 2000; Kim et al. 2009).