APP and Alzheimer disease: We have recently generated and characterized a knock-in mouse expressing a phospho-deficient PS1 (Psen1S367A/S367A, denoted Psen1KI/KI), which, when crossed with an AD mouse model (J20—mouse expressing human APP bearing Swedish and Indiana AD-causing mutations), exhibits a significant accumulation of Aβ independent of γ-secretase activity [20, 21].