APP and familial Alzheimer disease: The critical role of Aβ in the pathogenesis of AD is strongly supported by the identification of early-onset familial AD (FAD)-causing mutations within the genes encoding either the amyloid precursor protein (APP) itself or presenilin 1 and 2 (PS1 and PS2) that commonly alter the production of Aβ peptides in quantitative and qualitative ways (Bateman et al., 2011; Benilova et al., 2012; Katsnelson et al., 2016; De Strooper and Karran, 2016).