APP and Alzheimer disease: However, with a sufficient increase in the duration of the operation of the unconventionally activated AβPP-independent C99/iAβ generation pathway and consequent elevation of the baseline of the resumed accumulation of AβPP-derived iAβ (to levels still below the T1) (following the withdrawal of an unconventional stressor), the latter would inevitably cross the T1 threshold and AD would occur.