APP and Alzheimer disease: Indeed, it can be speculated that the RNA-dependent amplification of human AβPP mRNA does occur constitutively in healthy AD-unaffected neurons but the resulting chimeric mRNA product remains untranslated, “silent.” In such a case, the elicitation of the ISR, rather than activating the RNA-dependent mRNA amplification, enables translation of the otherwise “silent” uncapped C100-encoding chimeric mRNA.