APP and Alzheimer disease: The amyloid hypothesis, the prevalent theory of AD etiologies, suggests that the accumulation of pathological forms of β-amyloid (Aβ), produced by sequential cleavage of amyloid precursor protein (APP) by β- and γ-secretase, in the brain is the primary pathological process, driven by an imbalance between Aβ production and Aβ clearance.