The difference between this unconventional and conventional forms of AD is solely in the way the eIF2α is phosphorylated and the ISR elicited: in the conventional disease, the stressor activating the eIF2α kinases is AβPP-derived iAβ accumulated, in a decades-long process, over the critical threshold, whereas in unconventional AD eIF2α, kinases are activated and, consequently, the ISR elicited by stressors other than AβPP-derived iAβ. Here, EIF2A is linked to Alzheimer disease.