Plasma sEV TDP-43 levels were highest in ALS (median 45.45 pg ml−1, IQR [28.88−83.21]) compared with HC (9.47 pg ml−1, IQR [7.63−13.33], P < 0.00001), bvFTD (31.25 pg ml−1, IQR [14.45−41.09]) and PSP (9.09 pg ml−1, IQR [7.73−13.27], P < 0.00001) (Fig. 3a (sEV) and Supplementary Fig. 11a and Supplementary Table 3 (mEV)). This evidence concerns the gene TARDBP and amyotrophic lateral sclerosis.