APP and Alzheimer disease: The amyloid cascade hypothesis [3], or a modified amyloid β (Aβ) oligomer hypothesis [4], postulated that AD etiology stems from Aβ peptides (particularly the toxic and aggregation-prone Aβ1–42) [5] that are produced by two sequential amyloidogenic proteolytic cleavages of the amyloid precursor protein (APP), first by the β-site APP-cleaving enzyme 1 (BACE1) [6] followed by γ-secretase [7].