APP and Alzheimer disease: This process was first elucidated in studies of the pathogenesis of Alzheimer disease, in which the amyloid precursor protein (APP) is initially cleaved by β-secretase to generate an APP C-terminal fragment (CTF) that is subsequently cleaved by the intramembrane aspartyl protease γ-secretase, releasing amyloid β-protein (Aβ) from the membrane.