TARDBP and amyotrophic lateral sclerosis: Consistent with the absence of tau pathology, plasma EV 3R/4R tau ratios of all genetically confirmed cases were in the range of HC, ALS and ALS–FTD (Fig. 5b,c and Supplementary Fig. 22a,b) (HC: median sEV 1.02, IQR [0.96–1.06]; TDP-43 pathology group: median sEV 1.15, IQR [1.07–1.23], versus HC P > 0.9999; non-TDP-43/non-tau group: median sEV 0.92, IQR [0.84–1.15], versus HC P > 0.9999).