APP and Alzheimer disease: Initially, γ-secretase inhibitors (GSI), such as DAPT (N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester ), were used to target Aβ production for treatment of AD, but results were unsuccessful, in part because of rebound increases in PS-1 expression with continued aberrant processing of APP and possibly additional γ-secretase-independent PS-1 functions such as intracellular calcium signaling, autophagy degradation, and turnover of the important Wnt signaling cofactor β-catenin [11,13].