To date, 19 different AD causing mutations in the γ-secretase enzyme PSEN-2 have been reported and were shown to alter the APP processing by increasing both the total level of Aβ and the Aβ42/40 ratio [6,7], suggesting that the dysregulation of Aβ production from APP can be considered a common effect of these mutations. Here, PSEN2 is linked to Alzheimer disease.