γ-Secretase was originally identified as the protease that carried out the final cleavage to release the amyloid beta (Aβ) from the amyloid β precursor protein (APP) and was an early target for pharmacologic inhibition of Aβ by γ-secretase inhibitors (GSIs) in Alzheimer’s disease (AD) [1, 2]. Here, APP is linked to Alzheimer disease.