APP and Alzheimer disease: To summarize, in light of the above, in the ACH2.0 framework, AACD is defined as the symptomatic manifestation of the neuronal cell damage caused by AβPP-derived iAβ accumulated to the concentration range between the T0 and T1 thresholds [2], a process that evolves into AD if and when iAβ levels reach and cross the T1 threshold and activate the AβPP-independent iAβ generation pathway.