biostudies-literatureJellen LCMichael J. Fox Foundation for Parkinson's ResearchMichael J. Fox Foundation for Parkinson's Research116https://www.ebi.ac.uk/biostudies/studies/S-EPMC12056004biostudies-literatureUnknown11(1)We previously demonstrated that kynurenine pathway (KP) dysregulation associates with Parkinson's disease (PD) and its symptoms. Here, we profiled 16 KP-related markers in a second, independent cohort; plasma: n = 202 (116 PD ("OFF"), 86 controls); CSF: n = 183 (108, 75). Consistent with previous findings, we detected significantly higher concentrations of neurotoxic 3-hydroxykynurenine in plasma and lower concentrations of neuroprotective kynurenic acid along with higher neurotoxic quinolinic acid/kynurenic acid ratios in CSF of PD patients. Additionally, 10 markers showed sex-based differences, with more pronounced dysregulation in females. These 10 markers loaded to a single principal component linked to higher UPDRS I and II scores. Together, this suggests a composite signature of KP dNPJ Parkinson's diseaseSex differences in peripheral and central dysregulation of the kynurenine pathway in Parkinson's disease.PMC12056004MJFF-010296Kong LLewis MMMadaj ZHuang XBrundin LJohnson AIsaguirre CSheldon RDEscobar Galvis MLJellen LCSha QfalseSex differences in peripheral and central dysregulation of the kynurenine pathway in Parkinson's disease.We previously demonstrated that kynurenine pathway (KP) dysregulation associates with Parkinson's disease (PD) and its symptoms. Here, we profiled 16 KP-related markers in a second, independent cohort; plasma: n = 202 (116 PD ("OFF"), 86 controls); CSF: n = 183 (108, 75). Consistent with previous findings, we detected significantly higher concentrations of neurotoxic 3-hydroxykynurenine in plasma and lower concentrations of neuroprotective kynurenic acid along with higher neurotoxic quinolinic acid/kynurenic acid ratios in CSF of PD patients. Additionally, 10 markers showed sex-based differences, with more pronounced dysregulation in females. These 10 markers loaded to a single principal component linked to higher UPDRS I and II scores. Together, this suggests a composite signature of KP d2025-01-01T00:00:00Z2025 May2026-06-01T19:17:49.39Z2026-05-21T03:09:04.75ZS-EPMC120560044032876010.1038/s41531-025-00949-6