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.

Urinary biomarkers for amyotrophic lateral sclerosis: candidates, opportunities and considerations

“…A major issue with most of the studies is a discordance in collection protocols and how each is related to the clinical stage of disease, including time from diagnosis, and relationship to ALSFRS-R. 222 Meta-analysis including CSF and serum showed 16 pathways altered in ALS, 221 including caffeine metabolism, aminoacyl-tRNA biosynthesis and valine, leucine and isoleucine biosynthesis. However, it is not clear in the metabolomics studies if the samples were all taken from ALS patients with similar ALSFRS-R and time from diagnosis.…”

Liver’s influence on the brain through the action of bile acids

“…TUDCA activates GpBAR1, and inhibits the pro-inflammatory NFκB pathway in microglia, resulting in the inactivation of proinflammatory status in multiple sclerosis (MS) ( Bhargava et al, 2020 ). Despite a lack of consensus if BA disturbance is a response toward developing neuropathology or the initial cause of the neuropathology observed ( Dodge et al, 2021 ), the alteration of BAs content in the plasma can serve as an early diagnostic biomarker for AD ( Shao et al, 2020 ), PD ( Graham et al, 2018 ), MS ( Bhargava et al, 2020 ), and amyotrophic lateral sclerosis (ALS) ( Nakazato et al, 2022 ).…”

Taurine and Astrocytes: A Homeostatic and Neuroprotective Relationship

“…Taurine values have also been examined in biological samples such as blood and cerebrospinal fluid (CSF). A recent study found that taurine plasma levels correlated with the strength-duration time constant, an axonal excitability indicator, established to predict survival in amyotrophic lateral sclerosis (ALS) ( Nakazato et al, 2022 ). Furthermore, taurine was selected as a biomarker metabolite that helps to distinguish between patients with amnestic mild cognitive impairment and healthy controls ( Sun et al, 2020 ).…”