Dong Mei-Xue, Feng Xia, Xu Xiao-Min, Hu Ling, Liu Yang, Jia Si-Yu, Li Bo, Chen Wei, Wei You-Dong
Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Department of Neurology, Renmin Hospital of Wuhan University, Hubei General Hospital, Hubei, China.
Front Mol Neurosci. 2018 Aug 31;11:257. doi: 10.3389/fnmol.2018.00257. eCollection 2018.
Depression is a common comorbidity in Parkinson's disease (PD) but is underdiagnosed. We aim to investigate the altered metabolic pathways of Parkinson's disease-related depression (PDD) in plasma and to identify potential biomarkers for clinical diagnosis. Consecutive patients with PD were recruited, clinically assessed, and patients with PDD identified. Fasting plasma samples were collected from 99 patients and differentially expressed metabolites and proteins between patients with PDD and PD were identified using non-targeted liquid chromatography-mass spectrometry (LC-MS)-based metabolomics and tandem mass tag (TMT)-based proteomics analysis, followed by an integrated analysis. Based on the above results, enzyme-linked immune sorbent assay (ELISA) tests were then performed to identify potential biomarkers for PDD. In clinics, patients with PDD suffered less hypertension and had lower serum low-density lipoprotein cholesterol and apolipoprotein B levels when compared to the other patients with PD. A total of 85 differentially expressed metabolites were identified in metabolomics analysis. These metabolites were mainly lipids and lipid-like molecules, involved in lipid and glucose metabolic pathways. According to proteomics analysis, 17 differentially expressed proteins were identified, and 12 metabolic pathways were enriched, which were predominantly related to glucose metabolism. Integrated analysis indicated that altered lipid and glucose metabolism in PDD may induce cellular injury through oxidative stress. Additionally, plasma levels of several proteins were confirmed to be significantly altered and correlated with depressive severity. NOTCH2 may be a potential blood biomarker for PDD, with an optimal cut-off point of 0.91 ng/ml, a sensitivity value of 95.65%, and a specificity value of 81.58%. Depressive symptoms are associated with lipid and glucose metabolism in patients with PD and NOTCH2 may be a potential blood biomarker for the clinical diagnosis of PDD.
抑郁症是帕金森病（PD）常见的共病，但诊断不足。我们旨在研究帕金森病相关抑郁症（PDD）患者血浆中代谢途径的改变，并确定临床诊断的潜在生物标志物。招募连续的PD患者，进行临床评估，并确定PDD患者。收集了99例患者的空腹血浆样本，使用基于非靶向液相色谱-质谱（LC-MS）的代谢组学和基于串联质量标签（TMT）的蛋白质组学分析确定PDD患者和PD患者之间差异表达的代谢物和蛋白质，随后进行综合分析。基于上述结果，然后进行酶联免疫吸附测定（ELISA）试验以确定PDD的潜在生物标志物。在临床上，与其他PD患者相比，PDD患者患高血压的比例较低，血清低密度脂蛋白胆固醇和载脂蛋白B水平也较低。代谢组学分析共鉴定出85种差异表达的代谢物。这些代谢物主要是脂质和类脂分子，参与脂质和葡萄糖代谢途径。根据蛋白质组学分析，鉴定出17种差异表达的蛋白质，富集了12条代谢途径，主要与葡萄糖代谢有关。综合分析表明，PDD中脂质和葡萄糖代谢的改变可能通过氧化应激诱导细胞损伤。此外，证实几种蛋白质的血浆水平有显著改变，并与抑郁严重程度相关。NOTCH2可能是PDD的潜在血液生物标志物，最佳截断点为0.91 ng/ml，灵敏度值为95.65%，特异性值为81.58%。抑郁症状与PD患者的脂质和葡萄糖代谢有关，NOTCH2可能是PDD临床诊断的潜在血液生物标志物。
