GRN and Atrophy: GRN mutation carriers only showed significant atrophy at the CDR 0.5 stage – this was mainly cortical, affecting the DLPFC, and anterior insula, but there was also subcortical involvement of the presubiculum, a hippocampal region connected to the basal ganglia, frontal and parietal cortex, areas which are typically atrophic in GRN, as found here at the symptomatic stages and in other studies (Rohrer et al., 2015, Cash et al., 2018, Olney et al., 2020); and which typically show TDP-43 accumulation (Mann and Snowden, 2017).