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Combination of Two Blood Biomarkers Improves Diagnostic Accuracy in ALS
Despite modern imaging and genetic testing, diagnosing amyotrophic lateral sclerosis (ALS) remains challenging, particularly when distinguishing it from clinically similar neurodegenerative disorders. A new study led by the University Hospital Bonn (UKB) in cooperation with Alfried Krupp Hospital Essen now shows that combining two blood biomarkers – serum neurofilament light chain (sNfL) and cardiac troponin T (cTnT) – significantly improves diagnostic accuracy in ALS. The study results have been published in the journal Annals of Neurology.
Nov 3, 2025, 2:51:00 PM
Dr. Inka Väth
, Universitätsklinikum Bonn
Alessandro Winkler
Combination as a diagnostic advantage While sNfL is already established as a marker of neuroaxonal damage, it is not specific to ALS. cTnT, a classic cardiac biomarker, is also elevated in ALS patients due to muscle-specific changes – without any heart pathology. In the present study, the diagnostic value of both markers was evaluated individually as well as in combination. Study design and results Retrospectively, data from 293 ALS patients were compared with 85 patients with other neurodegenerative diseases and 29 healthy controls. Additionally, an independent cohort of 501 ALS patients was used to validate the results. Analysis using ROC curve methodology showed that the combined biomarker strategy significantly improves differentiation from other diseases – a crucial step forward for early diagnosis. ALS-Specific threshold for cTnT identified Another finding of the study is the identification of an ALS-specific threshold for cTnT at 8.35 ng/L – well below the established cardiological cutoff of 14 ng/L. Using this adjusted cutoff, the sensitivity of ALS diagnosis was further increased, allowing additional affected patients to be correctly identified. Prognostic value The study also showed that ALS patients with normal biomarker values (“biomarker-negative”) have significantly slower disease progression than “biomarker-positive” patients. Among study participants, the median disease duration in the biomarker-negative group was 73 months versus 18 months in the biomarker-positive group. Disease progression was also significantly slower. Conclusion “Our results demonstrate that combining sNfL and cTnT improves diagnostic accuracy in ALS and also provides valuable insights into disease progression,” says PD Dr. Patrick Weydt, Head of the ALS and Other Motor Neuron Disease Clinic at UKB. Dr. Weydt also conducts research at the University of Bonn. “In everyday clinical practice, it is crucial to reliably differentiate ALS from other neurological diseases at an early stage. The combination of sNfL and cTnT offers a real diagnostic advantage – using established, routine laboratory methods,” adds Dr. Torsten Grehl, Center for ALS and Other Motor Neuron Diseases at Alfried Krupp Hospital Essen. The dual biomarker strategy could help diagnose ALS earlier and more reliably in the future – and identify subgroups with different prognoses. The findings thus open new perspectives for personalized ALS diagnostics and therapy development. Participating institutions In addition to UKB, the University of Bonn, and DZNE, the study involved Alfried Krupp Hospital Essen, Charité – Universitätsmedizin Berlin, and the outpatient partners Soziotechnologie APST GmbH in Berlin. Publication: Paula Lindenborn et al.: Combination of serum neurofilament light chain and serum cardiac troponin T as biomarkers improves diagnostic accuracy in amyotrophic lateral sclerosis; Annals of Neurology; https://doi.org/10.1002/ana.78066