Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany.
Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany.
Cell Rep Med. 2022 Jun 21;3(6):100661. doi: 10.1016/j.xcrm.2022.100661.
Parkinson's disease (PD) is a growing burden worldwide, and there is no reliable biomarker used in clinical routines to date. Cerebrospinal fluid (CSF) is routinely collected in patients with neurological symptoms and should closely reflect alterations in PD patients' brains. Here, we describe a scalable and sensitive mass spectrometry (MS)-based proteomics workflow for CSF proteome profiling. From two independent cohorts with over 200 individuals, our workflow reproducibly quantifies over 1,700 proteins from minimal CSF amounts. Machine learning determines OMD, CD44, VGF, PRL, and MAN2B1 to be altered in PD patients or to significantly correlate with clinical scores. We also uncover signatures of enhanced neuroinflammation in LRRK2 G2019S carriers, as indicated by increased levels of CTSS, PLD4, and HLA proteins. A comparison with our previously acquired urinary proteomes reveals a large overlap in PD-associated changes, including lysosomal proteins, opening up new avenues to improve our understanding of PD pathogenesis.
帕金森病（PD）是全球日益加重的负担，迄今为止，临床上尚无可靠的生物标志物用于诊断。有神经症状的患者通常会采集脑脊液（CSF），CSF 应该能密切反映 PD 患者大脑的变化。在此，我们描述了一种基于质谱（MS）的可扩展和敏感的 CSF 蛋白质组分析工作流程。通过两个包含 200 多人的独立队列，我们的工作流程能够从最小量的 CSF 中重现定量超过 1700 种蛋白质。机器学习确定 OMD、CD44、VGF、PRL 和 MAN2B1 在 PD 患者中发生改变，或者与临床评分显著相关。我们还发现 LRRK2 G2019S 携带者的神经炎症增强特征，这表明 CTSS、PLD4 和 HLA 蛋白水平升高。与我们之前获得的尿液蛋白质组进行比较，揭示了 PD 相关变化的高度重叠，包括溶酶体蛋白，为改善我们对 PD 发病机制的理解开辟了新途径。
