BACE1 and Alzheimer disease: To summarize, in the composite therapeutic strategy for symptomatic AD, the transient inhibition of the neuronal integrated stress response carries out a double duty: It enables the production of BACE1 and BACE2 and thus ensures their availability, and disables the AβPP-independent C100/C99 generation pathway, thus abolishing the influx of iAβ (or C99) produced independently of AβPP and ensuring its efficient depletion.