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Phosphorylated tau (p-tau) species are elevated in serum in amyotrophic lateral sclerosis (ALS), where they may reflect peripheral nerve and muscle pathology. We aimed to investigate serum p-tau181 and p-tau217 as longitudinal biomarkers in adolescent and adult SMA and assessed associations with clinical parameters.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this retrospective multi-centre study, we assessed serum p-tau181 and p-tau217 levels in adults with 5q SMA under treatment with nusinersen or risdiplam, comparing levels with Alzheimer\u2019s disease (AD), amyotrophic lateral sclerosis (ALS) and non-neurodegenerative disease controls.<\/jats:p>\n                    <jats:p>Associations with motor function, respiratory capacity, creatine kinase (CK), and neurofilament light chain (NfL) were assessed using linear mixed-effects models adjusted for age and sex.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Serum p-tau181 was higher in SMA than in disease controls (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      = \u22120.48, 95%-CI \u22120.81 to \u22120.15), but lower than in ALS (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      = 0.99, 95%-CI 0.58 to 1.39) and AD (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      = 0.56, 95%-CI 0.11 to 1.00). P-tau181 declined from baseline to FUP2 (\u0394 median \u22121.80\u00a0pg\/mL, IQR \u22125.90 to 2.10); p-tau217 showed no longitudinal change. P-tau181 and p-tau217 were positively associated with motor function, functional status, respiratory capacity, and CK, with no association with NfL. In exploratory analyses, higher baseline p-tau181 was associated with greater HFMSE decline (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      = 1.79, 95%-CI 0.59 to 2.99).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Serum p-tau181 and p-tau217 appear to reflect ongoing muscle turnover in adult SMA, declining as muscle mass decreases. Higher baseline p-tau181 was associated with subsequent functional deterioration, suggesting potential utility as a biomarker of active denervation and disease monitoring.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00415-026-14194-1","type":"journal-article","created":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T06:43:23Z","timestamp":1792565003000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Serum p-tau181 and p-tau217 levels in adolescents and adults with 5q spinal muscular atrophy"],"prefix":"10.1007","volume":"273","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-0183-8357","authenticated-orcid":false,"given":"Caroline Deborah","family":"Stapf","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeljko","family":"Uzelac","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Iterbeke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur","family":"Guthknecht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Barba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Strube","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"K\u00f6lsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Kleeberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Kendzierski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Roos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Steinacker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samir","family":"Abu-Rumeileh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristl G.","family":"Claeys","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen","family":"Weishaupt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Mensch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4273-4267","authenticated-orcid":false,"given":"Markus","family":"Otto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,21]]},"reference":[{"key":"14194_CR1","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1016\/j.ncl.2015.07.004","volume":"33","author":"SJ Kolb","year":"2015","unstructured":"Kolb SJ, Kissel JT (2015) Spinal muscular atrophy. 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The other authors have no relevant financial or non-financial interests to disclose.","order":1,"name":"Ethics","label":"Conflicts of interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Eligible participants included patients with genetically confirmed 5q spinal muscular atrophy (SMA) (adults \u226518\u00a0years and minors <18\u00a0years), who provided written informed consent or their legal guardians. The study was conducted in accordance with Good Clinical Practice (GCP) guidelines. Ethical approval for the analysis of biomaterial and clinical data was obtained from the Ethics Committees of Martin Luther University Halle-Wittenberg, Germany (reference no. 2021\u2013101); Ulm University, Germany (reference no. 20\/10); and UZ\/KU Leuven, Belgium (reference no. S69981).","order":2,"name":"Ethics","label":"Ethical approval","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"672"}}