APP and Alzheimer disease: Pathological cleavage of APP by β-secretase occurs in sporadic AD, but missense mutations in APP such as K595N/M596L in the β-cleavage site can cause increased Aβ production and early onset AD (Benilova et al., 2012; Citron et al., 1992; Hardy and Selkoe, 2002; Selkoe and Hardy, 2016).