ABSTRACT Objective 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‐derived measures of disease aggressiveness (D50) and disease accumulation (rD50) in ALS. Methods 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 = 433) and an independent replication cohort (Bonn, n = 185). Results TnT levels were strongly associated with rD50‐defined disease phases in the discovery cohort (p < 0.001). While not all subgroup‐specific 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‐derived disease phases. sNfL concentrations demonstrated a significant inverse association with D50, supporting a relationship with disease aggressiveness across both cohorts (p < 0.001). Associations between TnT levels and D50‐defined disease aggressiveness were generally weaker and less consistent. Interpretation 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.
Julia Sellin, Sofia Waldorf, Janina von der Gablentz et al.· Annals of Clinical and Trans...· 0 citations
Background and Objectives CSF proteomics has emerged as a valuable strategy for identifying diagnostic and prognostic biomarkers in amyotrophic lateral sclerosis (ALS). However, the limited availability and volumes of CSF samples restrict the broader clinical application of CSF-based biomarker panels. To address this challenge, we investigated whether the novel nucleic acid-linked immuno-sandwich assay (NULISA) multiplex platform—capable of quantifying multiple neural, glial, and inflammatory markers from minimal biofluid volumes—could validate previously proposed biomarkers and identify additional candidates relevant to ALS. Methods Using this platform, we measured a targeted panel of 131 biomarkers in cohorts of patients with C9orf72-associated ALS, sporadic ALS (sALS), and matched healthy controls. Results The 6 markers neurofilament heavy chain (NEFH) and neurofilament light chain (NEFL), chitinases—particularly chitotriosidase-1 (CHIT1) and chitinase-3-like protein-1 (CHI3L1), and chemokines CCL2 and CCL3 were significantly elevated in both ALS groups compared with controls. These biomarkers correlated with disease progression and demonstrated strong diagnostic performance when combined into aggregate scores, as reflected by a high area under the receiver operating characteristic curve for ALS. Notably, C9orf72-ALS patients exhibited higher levels of the oxidative stress-related markers PRDX6 and ENO2, compared with sALS patients, suggesting a genotype-specific molecular signature. Discussion Overall, our findings support the use of a multiplexed panel of diverse, inflammatory, glial, and neurodegeneration-associated biomarkers as a complementary diagnostic and prognostic tool alongside established measurements of neurofilaments. This approach may enhance biomarker robustness while minimizing CSF volume requirements, thereby improving clinical feasibility in ALS research and care.
Karthik Baskar, Christina Steffke, S. Bernsen et al.· Neurology(R) neuroimmunology...· 0 citations