IDE and Alzheimer disease: There are three means of defense from Aβ42-dependent AD pathology: (1) to slow the rate of Aβ42 aggregation, (2) to decrease the production of Aβ42 by downregulating the activity of β- or γ-secretase, and (3) to enhance protease activity (such as neprilysin [115], an insulin-degrading enzyme [116]) against Aβ42.