Plasma EV TDP-43 levels distinguished ALS from all other groups with high diagnostic accuracy (AUC ≥ 0.91 versus HC, PSP, bvFTD in DESCRIBE; AUC ≥ 0.94 versus HC, PSP; and AUC ≥ 0.76 versus bvFTD in the Sant Pau cohort). Here, TARDBP is linked to amyotrophic lateral sclerosis.