In unconventional cases of AD, both approaches mentioned above are, apparently, utilized: in chronic encephalopathy it is the repeated trauma (i.e., the repeated elicitation of the ISR and a stepwise increase in the levels of iAβ produced independently of AβPP), whereas in chronic inflammation and prolonged viral and bacterial infections, it is a sufficient duration of the ISR elicitation, which ensures the accumulation of iAβ (produced in the AβPP-independent pathway) to levels exceeding the T1 threshold. This evidence concerns the gene APP and Alzheimer disease.