Plasma taurine is an axonal excitability-translatable biomarker for amyotrophic lateral sclerosis

Abstract

Although various body fluid biomarkers for amyotrophic lateral sclerosis (ALS) have been reported, no biomarkers specifically reflecting abnormalities in axonal excitability indices have currently been established. Capillary electrophoresis time-of-flight mass spectrometry and liquid chromatography time-of-flight mass spectrometry were used to perform a comprehensive metabolome analysis of plasma from seven ALS patients and 20 controls, and correlation analysis with disease phenotypes was then performed in 22 other ALS patients. Additionally, electrophysiological studies of motor nerve axonal excitability were performed in all ALS patients. In the ALS and control groups, levels of various metabolites directly associated with skeletal muscle metabolism, such as those involved in fatty acid β-oxidation and the creatine pathway, were detected. Receiver operating characteristic curve analysis of the top four metabolites (ribose-5-phosphate, N6-acetyllysine, dyphylline, 3-methoxytyrosine) showed high diagnostic accuracy (area under the curve = 0.971) in the ALS group compared with the control group. Furthermore, hierarchical cluster analysis revealed that taurine levels were correlated with the strength-duration time constant, an axonal excitability indicator established to predict survival. No significant effects of diabetes mellitus and treatment (Riluzole and Edaravone) on this relationship were detected in the study. Therefore, plasma taurine is a potential novel axonal excitability-translatable biomarker for ALS.