APP and Alzheimer disease: However, during the amyloidogenic pathway, APP is sequentially cleaved by β- and γ-secretases to produce N-terminal fragment of APP (sAPPβ) and C-terminal fragments (CTFβ, C99), and C99 further processes Aβ38, Aβ40, and Aβ42 fragments, which are the major pathologies of AD [3].