APP and Alzheimer disease: Only if and when AβPP-derived iAβ reaches the critical threshold and the AβPP-independent Aβ generation pathway and, consequently, the self-sustaining AD Engine (arched arrows-connected boxes in Figure 1) is activated (referred to henceforth as the symptomatic “second stage of AD”) does the disease commence, and “the first stage of AD” earns its name.