APP and Alzheimer disease: The amyloid cascade hypothesis of AD (Hardy and Allsop, 1991) states that aberrant cleavage of APP by γ-secretase results in the accumulation of cytotoxic oligomeric amyloid-β1-42 (Aβ1-42) which aggregates and forms β-sheet fibrillar structures that, in turn, clump together and generate extracellular amyloid plaques (Lukiw, 2012; Morris et al., 2014).