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Improper proteolytic processing of APP in Alzheimer’s disease. Under physiological conditions, APP is cleaved via α-secretase (α) followed by γ-secretase (γ) to generate non-amyloidogenic fragments. However, when neuronal activity is altered, APP is incorrectly cleaved by β-secretase (β) and γ-secretase to generate amyloidogenic Amyloid-β (Aβ), which leads to Alzheimer’s disease.
