APP and Alzheimer disease: Although AD has a complex pathophysiology, two hypotheseshavegained significant evidence: the amyloid cascade hypothesis (ACH)12−14 and the tau hyperphosphorylation hypothesis (THH).15−17 The amyloidogenic pathway results from the sequential cleavage ofthe amyloid precursor protein (APP) by β-secretase and γ-secretase.β-Secretase cleaves at the N-terminus of APP, while γ-secretasecleaves at its intramembranous domain.