He Haijun, Xiong Xi, Zheng Yi, Hou Jialong, Jiang Tao, Quan Weiwei, Huang Jiani, Xu Jiaxue, Chen Keke, Qian Jingjing, Cai Jinlai, Lu Yao, Lian Mengjia, Xie Chenglong, Luo Ji
Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Department of Physiology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
Front Aging Neurosci. 2025 Feb 26;17:1511272. doi: 10.3389/fnagi.2025.1511272. eCollection 2025.
The exact mechanisms of PD are unclear, but Parkin-mediated mitophagy dysfunction is believed to play a key role. We investigated whether blood levels of Parkin and other biomarkers are linked to the risk of developing PD.
Baseline blood measures of Parkin and other biomarkers, including Homocysteine, carcinoembryonic antigen, Urea, total proteins, total cholesterol, creatine kinase, and albumin, were collected from 197 clinically diagnosed Parkinson's disease participants and 107 age-matched healthy controls in Wenzhou Parkinson's Biomarkers and Living Characteristics study. We conducted bioinformatics analysis using three datasets from the GEO database: GSE90514 (Cohort 1: PD = 4, HC = 4), GSE7621 (Cohort 2: PD = 16, HC = 9), and GSE205450 (Cohort 3: PD = 69, HC = 81).
Using a bioinformatic approach, we identified dysregulated biological processes in PD patients with PRKN mutations. Compared to controls, significant abnormalities were observed in blood levels of Parkin, Hcy, total proteins, urea, albumin, and CEA in PD patients. A model incorporating Parkin, Hcy, total proteins, and urea effectively distinguished PD from healthy controls, achieving a higher accuracy (AUC 0.841) than other biomarker combinations. Gene set enrichment analysis suggested that pathways such as PINK1-Parkin-mediated mitophagy, urea cycle, cysteine degradation, and riboflavin metabolism may be involved in PRKN mutation. Additionally, the link between Parkin and PD was partially mediated by CEA and albumin, not by Hcy, total proteins, or urea.
Our findings indicate that blood Parkin levels may be a minimally invasive biomarker for PD diagnosis. The model, which included Parkin, Hcy, total proteins, and urea, effectively distinguished PD from HC with greater accuracy.
帕金森病（PD）的确切发病机制尚不清楚，但据信帕金蛋白介导的线粒体自噬功能障碍起关键作用。我们研究了帕金蛋白及其他生物标志物的血液水平是否与患PD的风险相关。
在温州帕金森生物标志物与生活特征研究中，收集了197名临床诊断为帕金森病的参与者和107名年龄匹配的健康对照者的帕金蛋白及其他生物标志物的基线血液检测指标，包括同型半胱氨酸、癌胚抗原、尿素、总蛋白、总胆固醇、肌酸激酶和白蛋白。我们使用来自基因表达综合数据库（GEO数据库）的三个数据集进行生物信息学分析：GSE90514（队列1：帕金森病患者=4例，健康对照者=4例）、GSE7621（队列2：帕金森病患者=16例，健康对照者=9例）和GSE205450（队列3：帕金森病患者=69例，健康对照者=81例）。
采用生物信息学方法，我们在携带PRKN基因突变的帕金森病患者中鉴定出失调的生物学过程。与对照组相比，帕金森病患者血液中的帕金蛋白、同型半胱氨酸、总蛋白、尿素、白蛋白和癌胚抗原水平存在显著异常。一个包含帕金蛋白、同型半胱氨酸、总蛋白和尿素的模型能够有效区分帕金森病患者和健康对照者，其准确率（曲线下面积为0.841）高于其他生物标志物组合。基因集富集分析表明，PINK1 - 帕金蛋白介导的线粒体自噬、尿素循环、半胱氨酸降解和核黄素代谢等途径可能与PRKN基因突变有关。此外，帕金蛋白与帕金森病之间的联系部分由癌胚抗原和白蛋白介导，而非同型半胱氨酸、总蛋白或尿素。
我们的研究结果表明，血液中的帕金蛋白水平可能是用于帕金森病诊断的一种微创生物标志物。包含帕金蛋白、同型半胱氨酸、总蛋白和尿素的模型能够更准确地有效区分帕金森病患者和健康对照者。
