APP and Alzheimer disease: The latter scenario (shown in panel B) plausibly accounts for unconventional AD caused by multiple events (such as multiple TBIs or chronic traumatic encephalopathy, CTE) or multiple transient occurrences of a condition (or combined events and conditions) that are capable of triggering unconventional activation of AβPP-independent pathway of generation of iAβ; when it crosses the T1 threshold, the pathway becomes self-sustainable and AD commences.