{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T19:17:47Z","timestamp":1791487067541,"version":"4.3.4"},"reference-count":15,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":265,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Region Stockholm","id":[{"id":"https:\/\/ror.org\/02zrae794","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Swedish ALS-fonden"},{"DOI":"10.13039\/501100007416","name":"Swedish Brain Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007416","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005701","name":"\u00c5hlen foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005701","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Frick Foundation and Frimurar stiftelse"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Plasma cardiac troponin T (cTnT) is widely used as a marker of myocardial injury, yet recent studies suggest elevations in amyotrophic lateral sclerosis (ALS). Whether these elevations reflect disease-associated skeletal muscle remodelling remains unresolved. In this translational study, we analysed longitudinal plasma cTnT in a large clinical cohort comprising 496 patients with ALS and 84 with benign fasciculation syndrome (BFS). To investigate the biological origin of circulating cTnT, we examined publicly available skeletal muscle transcriptomes from patients with ALS (n = 28) and healthy controls (n = 17), and quantified troponin isoform expression in skeletal muscle from SOD1G93A mice and wild-type littermates. Plasma cTnT was significantly higher in ALS than in BFS (median 18 versus 6\u2005ng\/L, P = 3.6 \u00d7 10\u221227), with 57% of patients with ALS exceeding the cardiologic threshold of 15\u2005ng\/L. Diagnostic performance was high [area under the curve (AUC) 0.87], with excellent specificity (94%). Longitudinal modelling revealed a progressive increase in cTnT in ALS whereas levels remained stable in BFS. Skeletal muscle transcriptomics demonstrated robust upregulation of TNNT2, encoding cardiac troponin T, in ALS muscle, while other troponin isoforms were unchanged. In SOD1G93A mice, severely affected gastrocnemius muscle exhibited isoform-specific remodelling, including 20-fold upregulation of Tnnt2 and slow-fibre troponins, alongside downregulation of fast skeletal isoforms. Across clinical, transcriptomic, and experimental data, elevated plasma cTnT in ALS is best explained by disease-associated skeletal muscle remodelling rather than cardiomyocyte injury. Plasma cTnT emerges as a dynamic and accessible biomarker in ALS capturing muscle involvement. Prospective incorporation of cTnT into clinical trials and evaluation across broader neuromuscular differentials are warranted.<\/jats:p>","DOI":"10.1093\/braincomms\/fcag358","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T11:37:37Z","timestamp":1790077057000},"source":"Crossref","is-referenced-by-count":0,"title":["Plasma cardiac troponin T as a marker of skeletal muscle involvement in amyotrophic lateral sclerosis"],"prefix":"10.1093","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0635-6377","authenticated-orcid":false,"given":"Linn","family":"\u00d6ijerstedt","sequence":"first","affiliation":[{"name":"Department of Clinical Neuroscience, Karolinska Institutet , SE-171 77 Stockholm ,","place":["Sweden"]},{"name":"Department of Neurology, Karolinska University Hospital , SE-171 76 Stockholm 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Neurology, Karolinska University Hospital , SE-171 76 Stockholm ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4412-0413","authenticated-orcid":false,"given":"Alexander","family":"Juto","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience, Karolinska Institutet , SE-171 77 Stockholm ,","place":["Sweden"]},{"name":"Department of Neurology, Karolinska University Hospital , SE-171 76 Stockholm ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanharib","family":"Chamoun","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience, Karolinska Institutet , SE-171 77 Stockholm ,","place":["Sweden"]},{"name":"Department of Neurology, Karolinska University Hospital , SE-171 76 Stockholm 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