These types of rare variants have the possibility to exercise a large effect on disease risk and often show a Mendelian inheritance pattern, thus being at the core of familial forms of many disorders; prominent examples are rare variants in APP, PSEN1, and PSEN2 in familial AD [5] or variants in MAPT, GRN and C9orf72 in frontotemporal dementia (FTD) [6]. Here, PSEN2 is linked to frontotemporal dementia.