This work highlights the higher performance of small EVs, which contrasts with the findings of Casarotto et al. and Sproviero et al. where, in a small number of cases, the difference in TDP-43 levels between both ALS or FTD cases and healthy controls was highest in large EVs (pelleted at 20,000 xg) and not detected in small EVs [73, 77]. The gene discussed is TARDBP; the disease is amyotrophic lateral sclerosis.