APP and Alzheimer disease: PKR and/or HRI kinases are activated, eIF2α phosphorylated at its Ser51, the neuronal ISR elicited, and the AβPP-independent C99 (and iAβ in this version of the ACH2.0) production pathway initiated, and iAβ reaches the AD pathology-causing range; when it crosses the T2 threshold, neurons commit apoptosis.