Remarkably, to date, any missense mutation in Mendelian gene domains harboring heterozygous causative mutations for autosomal dominant disorders such as familial AD and FTD (APP, PSEN1, PSEN2, and MAPT) has always been reported as pathogenic (Supplementary Table S12, http://www.molgen.ua.ac.be/ADMutations/). This evidence concerns the gene APP and frontotemporal dementia.