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. The gene discussed is NEFL; the disease is frontotemporal dementia.