In summary, with EV 3R/4R tau and EV TDP-43 we describe the first marker that specifically detects underlying molecular pathology in patients with ALS, FTD and FTD spectrum disorders, whereas previously suggested biomarkers reflect downstream effects such as neurodegeneration (NfL)61,62 or inflammation (glial fibrillary acidic protein)63,64. This evidence concerns the gene GFAP and amyotrophic lateral sclerosis.