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This study aims to investigate amino acid metabolic alterations in multiple sclerosis to identify potential biomarkers and understand their role in pathophysiology.

March 1, 2026Cumhuriyet Science Journal0 citationsOpen Access

Amino Acid Metabolism in Multiple Sclerosis: Analyzing Plasma and Cerebrospinal Fluid Profiles for Biomarker Discovery and Pathophysiological Insights

BÇBurhanettin Çiğdem SKSümeyra Kaplan HDHalef Okan Doğan

Key Points

This study aims to investigate amino acid metabolic alterations in multiple sclerosis to identify potential biomarkers and understand their role in pathophysiology.
Collected plasma and cerebrospinal fluid samples from MS patients and pseudotumor cerebri controls.
Measured amino acid concentrations using liquid chromatography-tandem mass spectrometry.
Conducted pathway analysis to assess biochemical disruptions associated with MS.
MS patients showed lower plasma tyrosine and higher CSF hydroxylysine and ornithine levels compared to controls.
Certain CSF amino acids correlated positively or inversely with immune cell counts and protein levels.
No CSF amino acids correlated with Expanded Disability Status Scale scores, but specific plasma amino acids did.

Abstract

Multiple sclerosis (MS) is a neuroinflammatory disease associated with involving metabolic disruptions. Although amino acid metabolism is linked to MS pathophysiology, its role remains unclear. This study investigates alterations in amino acid profiles to identify potential biomarkers for MS. Plasma and cerebrospinal fluid (CSF) samples were collected from MS patients and individuals with pseudotumor cerebri (PTC) as controls. Amino acid concentrations were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Compared to controls, MS patients exhibited lower plasma tyrosine levels and higher CSF hydroxylysine and ornithine levels. CSF 3-aminoisobutyric acid and valine correlated positively with lymphocyte/monocyte counts, while CSF β-alanine exhibited inverse correlations. Additionally, CSF β-alanine, homocitrulline, and citrulline were associated with CSF protein levels. Expanded Disability Status Scale (EDSS) scores were associated with plasma isoleucine, methionine, citrulline, and threonine—no CSF amino acids correlated with EDSS. Pathway analysis identified significant disruptions in phenylalanine-tyrosine-tryptophan biosynthesis, arginine biosynthesis, and ubiquinone pathway. Altered amino acid metabolism plays a critical role in MS pathogenesis. The observed correlations between immune cell counts and specific amino acids highlight their involvement in immune activation and neuroinflammation, suggesting that targeting specific molecular networks may offer therapeutic potential

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