Biochemical Differences in Cerebrospinal Fluid between Secondary Progressive and Relapsing⁻Remitting Multiple...

Area of Science:

• Neuroscience
• Metabolomics
• Biochemistry

Background:

• Multiple Sclerosis (MS) encompasses various subtypes, including relapsing-remitting (RRMS) and secondary progressive (SPMS).
• Understanding the pathophysiological distinctions between RRMS and SPMS is crucial for identifying progression biomarkers.
• Cerebrospinal fluid (CSF) metabolomics offers a window into central nervous system biochemical changes.

Purpose of the Study:

• To investigate the CSF metabolome differences between SPMS and RRMS patients.
• To identify potential CSF biomarkers indicative of MS disease progression.
• To correlate metabolic alterations with clinical and radiological disease measures.

Main Methods:

• High-resolution mass spectrometry (HRMS) was employed to analyze the CSF metabolome.
• Partial least squares discriminant analysis (PLS-DA) was used to identify significant biochemical differences.
• Metabolite levels were correlated with clinical disability, disease activity, and brain atrophy.

Main Results:

• Significant alterations in tryptophan metabolism were observed in SPMS patients, including changes in kynurenate, 5-hydroxytryptophan, 5-hydroxyindoleacetate, and N-acetylserotonin.
• SPMS patients exhibited altered kynurenine and indole-3-acetate levels compared to RRMS and control groups.
• Perturbations in pyrimidine metabolism, specifically uridine, deoxyuridine, thymine, and glutamine, were noted in SPMS patients.
• Pyrimidine metabolites significantly correlated with disability, disease activity, and brain atrophy in SPMS.

Conclusions:

• CSF metabolomic profiling reveals distinct biochemical pathways altered in SPMS compared to RRMS.
• Tryptophan and pyrimidine metabolism are significantly perturbed in SPMS, with pyrimidine metabolites serving as potential progression markers.
• These findings contribute to understanding the molecular pathogenesis of SPMS and support the use of CSF metabolomics for tracking disease progression.