APP and Alzheimer disease: Indeed, overwhelming evidence—especially from familial forms of early-onset AD (FAD)—has shown that the β- and γ-secretase-mediated proteolytic breakdown of APP, which generates neurotoxic amyloid-beta (Aβ) peptides, primarily of 38, 40, or 42 amino acid lengths (Aβ38, Aβ40, and Aβ42) [2].