APP and Alzheimer disease: In addition to the role of γ-secretase in the generation of Aβ from APP, it also proteolyzes many other type I integral membrane proteins, in particular the Notch receptor, which plays a role in many essential steps during cell differentiation.176 So targeting γ-secretase as a significant approach to the treatment of AD should avoid affecting Notch signaling in order to show a good safety profile.177