Plasma sEV TDP-43 distinguished ALS from HC, PSP and bvFTD with AUC values of 0.94, CI [0.892–0.981], 0.96, CI [0.910–0.991] and 0.76, CI [0.687–0.832] (Supplementary Table 14), and ALS–FTD from HC, PSP and bvFTD groups (AUC 0.98, CI [0.946–0.999], 0.99, CI [0.955–1.000] and 0.82, CI [0.745–0.881]) (Supplementary Fig. 19a–g (sEV), Supplementary Fig. 18b–h) (mEV) and Supplementary Table 14). Here, TARDBP is linked to frontotemporal dementia.