Jellen Leslie C, Escobar Galvis Martha L, Sha Qiong, Isaguirre Christine, Johnson Amy, Madaj Zach, Lewis Mechelle M, Sheldon Ryan D, Kong Lan, Huang Xuemei, Brundin Lena
Department of Neurology, Translational Brain Research Center, Penn State University-Milton S. Hershey Medical Center, Hershey, PA, USA.
Office of the Cores, Van Andel Institute, Grand Rapids, MI, USA.
NPJ Parkinsons Dis. 2025 May 6;11(1):116. doi: 10.1038/s41531-025-00949-6.
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 dysregulation in PD that is associated with worse symptoms and more prevalent in women. This work shows that KP dysregulation in peripheral and central compartments is linked to symptom severity in PD and warrants further systematic studies unraveling sex-dependent metabolic differences.
我们之前证明，犬尿氨酸途径（KP）失调与帕金森病（PD）及其症状相关。在此，我们在第二个独立队列中分析了16种与KP相关的标志物；血浆：n = 202（116例PD患者（“关”期），86例对照）；脑脊液：n = 183（108例，75例）。与之前的研究结果一致，我们在PD患者的血浆中检测到神经毒性3-羟基犬尿氨酸浓度显著升高，脑脊液中神经保护性犬尿酸浓度降低，同时神经毒性喹啉酸/犬尿酸比值升高。此外，10种标志物显示出基于性别的差异，女性的失调更为明显。这10种标志物加载到一个与较高的统一帕金森病评定量表（UPDRS）I和II评分相关的单一主成分上。总之，这表明PD中KP失调的综合特征与更严重的症状相关，且在女性中更为普遍。这项研究表明，外周和中枢部分的KP失调与PD的症状严重程度相关，值得进一步开展系统性研究以揭示性别依赖性代谢差异。
