In contrast, in prevention of unconventional AD the AβPP-independent iAβ production pathway has already been unconventionally activated, and to be effective BACE activation-mediated degradation of iAβ must be combined with the suppression of the neuronal ISR (or with the inhibition of the AβPP-independent iAβ production pathway by other means). Here, BACE1 is linked to Alzheimer disease.