APP and Alzheimer disease: APP, a major source of Aβ in AD, can be cleaved by α- and γ-secretase at the plasma membrane to form soluble APP α (sAPPα) through non-amyloidogenic pathway.338 After endocytosis, APP can be cleaved by β- and γ-secretase at the early endosomes to form Aβ through an amyloidogenic pathway.