ArticleEuropean journal of neurology2026
Protein Biomarkers in Risk and Prognosis of Amyotrophic Lateral Sclerosis.
Article in European journal of neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundPlasma and cerebrospinal fluid (CSF) protein biomarkers in amyotrophic lateral sclerosis (ALS) may provide insight into disease mechanisms and yield clinically useful biomarkers.
methodsOverall, 363 proteins in plasma and CSF from 198 patients with ALS and 125 matched controls were profiled using Olink assays. Associations with disease status, survival, and functional decline, as well as longitudinal biomarker stability across the disease course were assessed, together with network and enrichment analyses. ALS risk-associated biomarkers were externally validated in the UK Biobank (UKB).
resultsOverall, 125 proteins were significantly associated with at least one outcome (i.e., case status, risk, survival, or functional decline), and 21 were associated with three or more outcomes. NEFL was the most robust biomarker in plasma and CSF, alongside TNFRSF12A in plasma and CSF, EDA2R in plasma, and FABP4 in plasma and CSF. Most biomarkers remained stable longitudinally across the disease course. ALS risk-associated biomarkers were replicated in UKB, in which > 3000 plasma proteins were measured in 52,990 participants, including 298 with ALS. Network and enrichment analyses highlighted their roles in immune response and extracellular-matrix remodeling, and their enrichments in the brain and T-cell subsets. Construction of an ALS risk-prediction model achieved an ROC-AUC of 0.72 in the UKB validation cohort.
conclusionsThese findings suggest candidate protein biomarkers for ALS risk stratification, early detection, and clinical therapeutic monitoring.
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