PSEN1 and Alzheimer disease: The close link between genetic mutations and disorders associated with AD (mutations of presenilin 1 (PS1), presenilin 2 (PS2), amyloid beta precursor protein (APP), and Trisomy 21) and the accumulation of Aβ strongly implicates this molecule as a pathological driver in AD, but there is controversy over whether Aβ accumulation alone indicates inevitable progression to AD.