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Neurofilament light chain (NFL) and phosphorylated neurofilament heavy chain (pNFH) are elevated in ALS patients. We retrospectively quantified cerebrospinal fluid (CSF) NFL, CSF pNFH and plasma NFL in stored samples that were collected at the diagnostic work-up of ALS patients (n\u2009=\u2009234), ALS mimics (n\u2009=\u200944) and controls (n\u2009=\u20099). We assessed the diagnostic performance, prognostication value and relationship to the site of onset and genotype. CSF NFL, CSF pNFH and plasma NFL levels were significantly increased in ALS patients compared to patients with neuropathies &amp; myelopathies, patients with myopathies and controls. Furthermore, CSF pNFH and plasma NFL levels were significantly higher in ALS patients than in patients with other MNDs. Bulbar onset ALS patients had significantly higher plasma NFL levels than spinal onset ALS patients. ALS patients with\n                    <jats:italic>C9orf72HRE<\/jats:italic>\n                    \u00a0mutations had significantly higher plasma NFL levels than patients with\u00a0\n                    <jats:italic>SOD1<\/jats:italic>\n                    \u00a0mutations. Survival was negatively correlated with all three biomarkers. Receiver operating characteristics showed the highest area under the curve for CSF pNFH for differentiating ALS from ALS mimics and for plasma NFL for estimating ALS short and long survival. All\u00a0three biomarkers have diagnostic value in differentiating ALS from clinically relevant ALS mimics. Plasma NFL levels can be used to differentiate between clinical and genetic ALS subgroups.\n                  <\/jats:p>","DOI":"10.1038\/s41598-021-01499-6","type":"journal-article","created":{"date-parts":[[2021,11,11]],"date-time":"2021-11-11T06:06:09Z","timestamp":1636610769000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":85,"title":["Neurofilaments can differentiate ALS subgroups and ALS from common diagnostic mimics"],"prefix":"10.1038","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9347-0364","authenticated-orcid":false,"given":"Arvin","family":"Behzadi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7920-2884","authenticated-orcid":false,"given":"Fani","family":"Pujol-Calder\u00f3n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2369-4319","authenticated-orcid":false,"given":"Anton E.","family":"Tjust","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0838-5526","authenticated-orcid":false,"given":"Anna","family":"Wuolikainen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1213-9953","authenticated-orcid":false,"given":"Kina","family":"H\u00f6glund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2911-6026","authenticated-orcid":false,"given":"Karin","family":"Forsberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2708-7372","authenticated-orcid":false,"given":"Erik","family":"Portelius","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1890-4193","authenticated-orcid":false,"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3930-4354","authenticated-orcid":false,"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0094-5429","authenticated-orcid":false,"given":"Peter Munch","family":"Andersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,11,11]]},"reference":[{"key":"1499_CR1","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1038\/nrneurol.2014.184","volume":"10","author":"B Swinnen","year":"2014","unstructured":"Swinnen, B. & Robberecht, W. 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F.P.C. declares no disclosures relevant to the manuscript. A.E.T. declares no disclosures relevant to the manuscript. A.W. declares no disclosures relevant to the manuscript. K.H. declares no disclosures relevant to the manuscript. K.F. declares no disclosures relevant to the manuscript. E.P. declares no disclosures relevant to the manuscript. K.B. served as a consultant, at advisory boards, or at data monitoring committees for Abcam, Axon, Biogen, JOMDD\/Shimadzu. Julius Clinical, Lilly, MagQu, Novartis, Roche Diagnostics, and Siemens Healthineers, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program. H.Z. reports that he has served at scientific advisory boards for Denali, Roche Diagnostics, Wave, Samumed, Siemens Healthineers, Pinteon Therapeutics and CogRx, has given lectures in symposia sponsored by Fujirebio, Alzecure and Biogen, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program. P.M.A. reports grants from the Swedish Research Council, the Swedish Brain Foundation, the Knut and Alice Wallenberg Foundation, the Ulla-Carin Lindquist Foundation; has been\/is a consultant for Biogen, Orphazyme A\/S, Hoffman la Roche\/Genentech and Regeneron on matters regarding ALS genetics and clinical trials.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"22128"}}