{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T06:37:55Z","timestamp":1791959875656,"version":"4.3.4"},"reference-count":32,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T00:00:00Z","timestamp":1738800000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000098","name":"Clinical Center","doi-asserted-by":"publisher","award":["5P01NS084974"],"award-info":[{"award-number":["5P01NS084974"]}],"id":[{"id":"10.13039\/100000098","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005339","name":"American Academy of Neurology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005339","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>We performed a pilot screen to assess the utility of the NULISA\u2122 (Nucleic\u2010acid\u2010Linked Immuno\u2010Sandwich Assay) platform in the identification of amyotrophic lateral sclerosis (ALS) biomarkers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Plasma from 86 individuals (48 ALS, 18 asymptomatic C9<jats:italic>orf<\/jats:italic>72 repeat expansion carriers (AsymC9), and 20 healthy controls) was analyzed via a multiplexed NULISA\u2122 assay that includes 120 neurodegeneration\u2010associated proteins. Statistical analysis of NULISA\u2122 results was performed to identify proteins differentially expressed in plasma and their correlation with disease\u2010associated parameters.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>ALS plasma showed elevation of the established biomarkers, neurofilament light chain (NEFL) and neurofilament heavy chain (NEFH). Compared to controls and AsymC9, microtubule\u2010associated protein tau (MAPT), phosphorylated tau 181 (pTau181), phosphorylated tau 217 (pTau217), phosphorylated tau 231 (pTau231), and phosphorylated TDP\u201043 (pTDP\u201043) were elevated in ALS.\u2009NEFL levels positively correlated with pTau181, pTau217, pTau231, and pTDP\u201043.\u2009MAPT and pTDP\u201043 were also correlated with pTau181, pTau217 and pTau231. Elevated pTau was negatively correlated with survival and ALSFRS\u2010R. Spinal onset ALS was associated with higher pTau181, pTau217, and pTau231.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>We confirm previous reports showing elevated pTau181 in ALS plasma and show elevation of other phosphorylated tau forms, pTau217 and pTau231, typically observed in Alzheimer's disease. We provide preliminary data showing the detection and elevation of pTDP\u201043\u2010409\/410 in a subset of ALS samples compared to healthy controls. Neurofilament and tau levels are highly correlated suggesting their elevation may reflect a common pathology and disease state. Total and phosphorylated tau are correlated with multiple disease measures, such as ALS duration, ALSFRS\u2010R, and site of onset.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.70001","type":"journal-article","created":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T18:59:41Z","timestamp":1738868381000},"page":"714-723","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["<scp>ALS<\/scp> plasma biomarkers reveal neurofilament and <scp>pTau<\/scp> correlate with disease onset and progression"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2227-884X","authenticated-orcid":false,"given":"Eleanor V.","family":"Thomas","sequence":"first","affiliation":[{"name":"Department of Neurology Emory University  Atlanta Georgia 30322 USA"},{"name":"Center for Neurodegenerative Diseases Emory University  Atlanta Georgia 30322 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