APOE and Alzheimer disease: Mutations in the genes such as amyloid precursor protein (APP), presenilin-1 (PSEN1), presenilin-2 (PSEN2), and apolipoprotein E (APOE) are the key threat to Aβ aggregation and clearance that encourage early-onset AD (Rogaev et al., 1995; Sherrington et al., 1995; Page et al., 1996; Scheuner et al., 1996; Rovelet-Lecrux et al., 2006; Kline, 2012).