In this study, we aimed to evaluate modifiers of structural brain changes in presymptomatic mutation carriers from a large international cohort of subjects at risk for genetic FTD, investigating the effect of (i) pathogenetic mutation, i.e. MAPT, GRN and C9orf72 carriers versus non-carriers; (ii) cognitive reserve, as measured by years of formal schooling; and (iii) TMEM106B rs1990622 genotype, and their interaction, on grey matter volume. This evidence concerns the gene TMEM106B and frontotemporal dementia.