Less than 1% of Alzheimer's disease cases are familial, with autosomal dominant mutations described in only three genes that lead to early onset disease; APP, presenilin 1 (PSEN1) and presenilin 2 (PSEN2), both of the latter encoding components of the γ-secretase pathway (Schonrock and Gotz, 2012). Here, PSEN2 is linked to early-onset autosomal dominant Alzheimer disease.