{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T07:02:31Z","timestamp":1784876551724,"version":"3.55.0"},"reference-count":31,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Amyotrophic lateral sclerosis (ALS) is a clinically heterogeneous neurodegenerative disease requiring reliable biomarkers to improve patient stratification and trial design. While serum neurofilament light chain (sNfL) reflects neuroaxonal stress and disease aggressiveness, troponin T (TnT) may capture complementary aspects of neuromuscular involvement. We assessed the associations of TnT and sNfL with D50\u2010derived measures of disease aggressiveness (D50) and disease accumulation (rD50) in ALS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this retrospective observation, TnT and sNfL levels from ALS patients in two independent German cohorts were analyzed using the D50 disease progression model; discovery cohort (Essen,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009433) and an independent replication cohort (Bonn,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009185).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      TnT levels were strongly associated with rD50\u2010defined disease phases in the discovery cohort (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). While not all subgroup\u2010specific associations were replicated, the overall relationship between TnT and disease accumulation was supported in the independent replication cohort. In contrast, sNfL showed no consistent relationship with rD50\u2010derived disease phases. sNfL concentrations demonstrated a significant inverse association with D50, supporting a relationship with disease aggressiveness across both cohorts (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Associations between TnT levels and D50\u2010defined disease aggressiveness were generally weaker and less consistent.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>TnT was associated with measures of disease accumulation (rD50), whereas sNfL was more closely associated with disease aggressiveness (D50). Our results suggest that TnT and sNfL capture different dimensions of disease status within the D50 framework. Further longitudinal studies are needed to determine whether combining these biomarkers improves disease stratification or prognostic assessment in clinical practice and therapeutic trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acn3.70499","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T06:31:33Z","timestamp":1784874693000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Troponin T and Neurofilament Light Chain Levels as Complementary Biomarkers of Disease Accumulation and Aggressiveness in Amyotrophic Lateral Sclerosis"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-3893-9427","authenticated-orcid":false,"given":"Julia","family":"Sellin","sequence":"first","affiliation":[{"name":"University of Luebeck, Precision Neurology of Neuromuscular and Motor Neuron Disease  Luebeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Waldorf","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases, Center for Neurology University Hospital Bonn  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0647-5923","authenticated-orcid":false,"given":"Janina","family":"von der Gablentz","sequence":"additional","affiliation":[{"name":"University of Luebeck, Precision Neurology of Neuromuscular and Motor Neuron Disease  Luebeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torsten","family":"Grehl","sequence":"additional","affiliation":[{"name":"Department of Neurology Alfried Krupp Hospital  Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huelya","family":"Nazlican","sequence":"additional","affiliation":[{"name":"Department of Neurology Alfried Krupp Hospital  Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Meyer","sequence":"additional","affiliation":[{"name":"Department of Neurology, Center for ALS and Other Motor Neuron Disorders Charite\u2010Universitaetsmedizin Berlin, Corporate Member of Freie Universitaet Berlin, Humboldt\u2010Universitaet Zu Berlin and Berlin Institute of Health  Berlin Germany"},{"name":"Ambulanzpartner Soziotechnologie APST GmbH  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Grosskreutz","sequence":"additional","affiliation":[{"name":"University of Luebeck, Precision Neurology of Neuromuscular and Motor Neuron Disease  Luebeck Germany"},{"name":"University of Luebeck, Excellence Cluster for Precision Medicine in Inflammation  Luebeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2344-5662","authenticated-orcid":false,"given":"Patrick","family":"Weydt","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases, Center for Neurology University Hospital Bonn  Bonn Germany"},{"name":"German Center for Neurodegenerative Diseases  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7485-2626","authenticated-orcid":false,"given":"Sarah","family":"Bernsen","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases, Center for Neurology University Hospital Bonn  Bonn Germany"},{"name":"Department of Neurology, Center for ALS and Other Motor Neuron Disorders Charite\u2010Universitaetsmedizin Berlin, Corporate Member of Freie Universitaet Berlin, Humboldt\u2010Universitaet Zu Berlin and Berlin Institute of Health  Berlin Germany"},{"name":"German Center for 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