{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T06:39:36Z","timestamp":1783579176314,"version":"3.55.0"},"reference-count":33,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T00:00:00Z","timestamp":1777766400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T00:00:00Z","timestamp":1777766400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["P30AG062421"],"award-info":[{"award-number":["P30AG062421"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Muscle and Nerve"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction\/Aims<\/jats:title>\n                    <jats:p>Reliable biomarkers for amyotrophic lateral sclerosis (ALS) remain limited. Although previous studies have shown altered cerebrospinal fluid (CSF) tau measures in ALS, the clinical relevance of plasma tau species as biomarkers remains unclear. Here, we sought to determine whether total tau, tau phosphorylated at T181 (pTau\u2010T181), and their ratio are altered in ALS and whether these measures correlate with disease progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Plasma samples were obtained from two independent cohorts from the Northeast ALS Consortium (NEALS) Biofluid Repository (cohort 1:\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200976 ALS and\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200952 healthy controls [HC]; cohort 2:\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200998 ALS and\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200990 HC). Cohort 1 (mean age ALS 61.8\u2009years; 63% male) included longitudinal samples; cohort 2 (mean age ALS 45.8\u2009years; 51% male) was cross\u2010sectional. Tau measures were quantified using Quanterix Simoa (cohort 1) and Meso Scale Discovery (MSD) (cohort 2) platforms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In cohort 1, total tau was lower in ALS versus HC (0.88 vs. 1.49\u2009pg\/mL), whereas pTau\u2010T181 (30.29 vs. 12.97\u2009pg\/mL) and pTau\u2010T181:tau ratio (52.07 vs. 13.18\u2009pg\/mL) were higher. In cohort 2, total tau (40.07 vs. 25.85\u2009pg\/mL), pTau\u2010T181 (6.77 vs. 2.18\u2009pg\/mL), and their ratio (0.37 vs. 0.098\u2009pg\/mL) were elevated in ALS. Plasma measures in cohort 1 did not correlate with decline on the revised ALS Functional Rating Scale (ALSFRS\u2010R). Brain\u2010derived tau (BD\u2010tau) was elevated in ALS (10.07 vs. 5.65\u2009pg\/mL) in a subset of samples from cohort 1.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Collectively, plasma pTau\u2010T181 levels are consistently elevated in ALS, supporting future studies to define its potential utility as an ALS biomarker.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mus.70266","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T05:40:46Z","timestamp":1777873246000},"page":"139-148","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Phosphorylated Tau at Threonine 181 Is Elevated in Amyotrophic Lateral Sclerosis Plasma"],"prefix":"10.1002","volume":"74","author":[{"given":"Tiziana","family":"Petrozziello","sequence":"first","affiliation":[{"name":"Sean M. Healey &amp; AMG Center for ALS at Mass General, Massachusetts General Hospital  Boston Massachusetts USA"},{"name":"Lurie Center for Autism, Department of Pediatrics Massachusetts General Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan","family":"Mizerak","sequence":"additional","affiliation":[{"name":"Amylyx Pharmaceuticals Inc.  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aparna","family":"Krishnamoorthy","sequence":"additional","affiliation":[{"name":"Biostatistics Center, Department of Medicine Massachusetts General Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel A.","family":"Donahue","sequence":"additional","affiliation":[{"name":"Department of Neurology Massachusetts General Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayleen L.","family":"Castillo Torres","sequence":"additional","affiliation":[{"name":"Sean M. Healey &amp; AMG Center for ALS at Mass General, Massachusetts General Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranee Zara B.","family":"Monsanto","sequence":"additional","affiliation":[{"name":"Sean M. Healey &amp; AMG Center for ALS at Mass General, Massachusetts General Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno L.","family":"Hammerschlag","sequence":"additional","affiliation":[{"name":"Department of Neurology Massachusetts General Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah A.","family":"Webster","sequence":"additional","affiliation":[{"name":"Department of Neurology Massachusetts General Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Becky","family":"Fillingham","sequence":"additional","affiliation":[{"name":"Sean M. Healey &amp; AMG Center for ALS at Mass General, Massachusetts General Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pia","family":"Kivis\u00e4kk","sequence":"additional","affiliation":[{"name":"Department of Neurology Massachusetts General Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie","family":"Timmons","sequence":"additional","affiliation":[{"name":"Amylyx Pharmaceuticals Inc.  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Fox","sequence":"additional","affiliation":[{"name":"Amylyx Pharmaceuticals Inc.  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven E.","family":"Arnold","sequence":"additional","affiliation":[{"name":"Department of Neurology Massachusetts General Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Cohen","sequence":"additional","affiliation":[{"name":"Amylyx Pharmaceuticals Inc.  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Klee","sequence":"additional","affiliation":[{"name":"Amylyx Pharmaceuticals Inc.  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0505-1168","authenticated-orcid":false,"given":"Sabrina","family":"Paganoni","sequence":"additional","affiliation":[{"name":"Sean M. 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