The rate of accumulation of AβPP-derived iAβ via its intraneuronal retention or through the cellular uptake of secreted extracellular Aβ, both occurring physiologically, could be (albeit not always; see below) sufficient to activate PKR and/or HRI and thus trigger phosphorylation of eIF2α and elicitation of the neuronal integrated stress response but it is patently insufficient to support the accretion of AβPP-derived iAβ to the AD pathology-causing levels. Here, EIF2A is linked to Alzheimer disease.