APP and Alzheimer disease: In these models, the first stage, elicitation of the ISR, is enacted either by iAβ produced from amplification-ineligible AβPP mRNA expressed by the exogenous transgenes (the current transgenic AD models are, in fact, the “first-stage” models), by iAβ42 expressed from C100-encoding transgenes, or by various stressors other than iAβ.