Mutations at or near the cleavage sites of β- and γ-secretase [70,71] or the mutations of γ-secretase constituents, Presenilin-1 (Psen1) and Presenilin-2 (Psen2) [72], result in increased production of Aβ and consequently lead to early onset of AD [73]. Here, PSEN1 is linked to Alzheimer disease.