Altered Cerebrospinal Fluid Tryptophan–Kynurenine Pathway Metabolism in Multiple System Atrophy

BACKGROUND: Alterations in tryptophan-kynurenine (TRP-KYN) metabolism, which is associated with neuroinflammation, remain unclear in multiple system atrophy (MSA). OBJECTIVE: The aim was to investigate cerebrospinal fluid (CSF) TRP metabolites in MSA and their associations with other biomarkers. METHODS: A total of 51 patients with MSA and 56 controls were included. CSF TRP metabolites, such as KYN, quinolinic acid (QA), and kynurenic acid (KA), along with neurofilament light chain (NfL), glycoprotein nonmetastatic melanoma protein B (GPNMB), and soluble triggering receptor expressed on myeloid cells 2 (sTREM2), were analyzed. RESULTS: Patients with MSA exhibited higher levels of QA, a neuroinflammatory marker, and lower levels of KA, a neuroprotective marker, yielding an elevated QA-to-KA ratio. Neither QA nor KA correlated with clinical scores. GPNMB, sTREM2, and NfL were increased; however, these markers were independent of KYN pathway metabolites. CONCLUSIONS: MSA exhibited a significant imbalance in KYN metabolism, suggesting a shift toward inflammatory processes distinct from classic neuroinflammatory markers. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.