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In contrast, the clinical and biological significance of cardiac troponin T (cTnT) in ALS is not fully understood. We aimed to evaluate the relationship between plasma cTnT and disease aggressiveness, progression stage, and clinical phenotype in comparison with NfL.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Plasma cTnT and cerebrospinal fluid (CSF) NfL were analysed at diagnosis in a population-based cohort of 526 patients with ALS. Disease aggressiveness was modelled using the D50 framework, which quantifies the time taken to lose 50% of functional capacity (ALSFRS-R) and normalises individual disease trajectories. Biomarker associations with disease aggressiveness, phase, and clinical variables were assessed through group comparisons, logistic and linear regression, and receiver operating characteristic analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Neurofilament light chain in CSF was strongly associated with disease aggressiveness, with higher levels in patients with more aggressive disease. In contrast, plasma hs-cTnT did not correlate with D50. Across disease phases, CSF NfL remained relatively stable, whereas plasma hs-cTnT increased with advancing rD50, suggesting accumulation with disease progression. Plasma hs-cTnT levels were higher in patients with spinal compared to bulbar onset. Combined biomarker models improved sensitivity and negative predictive value for identifying less aggressive disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Plasma hs-cTnT and CSF NfL capture distinct but complementary dimensions of ALS pathology. While NfL reflects disease aggressiveness, hs-cTnT aligns with disease phase and clinical phenotype, supporting its use as a complementary biomarker for ALS characterisation and monitoring.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00415-026-14002-w","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T15:49:11Z","timestamp":1785167351000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Plasma cardiac troponin T complements neurofilament light chain by reflecting disease phase and phenotypic variation in amyotrophic lateral sclerosis"],"prefix":"10.1007","volume":"273","author":[{"given":"Julia","family":"Sellin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0635-6377","authenticated-orcid":false,"given":"Linn","family":"\u00d6ijerstedt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janina","family":"von der Gablentz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanharib","family":"Chamoun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulf","family":"Kl\u00e4ppe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rayomand","family":"Press","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin","family":"Samuelsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Grosskreutz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Ingre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"issue":"1035","key":"14002_CR1","doi-asserted-by":"publisher","first-page":"1048","DOI":"10.1001\/jamaneurol.2019.1534","volume":"76","author":"C Bridel","year":"2019","unstructured":"Bridel C, van Wieringen WN, Zetterberg H, Tijms BM, Teunissen CE, and the NFL Group (2019) Diagnostic value of cerebrospinal fluid neurofilament light protein in neurology: a systematic review and meta-analysis. 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