Department of Neurology, University Medical Center Goettingen, Goettingen, Germany.
Department of Experimental Neurodegeneration, Center for Biostructural Imaging of Neurodegeneration, University Medical Center Goettingen, Goettingen, Germany.
Mov Disord. 2023 Sep;38(9):1585-1597. doi: 10.1002/mds.29497. Epub 2023 Jul 14.
Parkinson's disease (PD) biomarkers are needed by both clinicians and researchers (for diagnosis, identifying study populations, and monitoring therapeutic response). Imaging, genetic, and biochemical biomarkers have been widely studied. In recent years, extracellular vesicles (EVs) have become a promising material for biomarker development. Proteins and molecular material from any organ, including the central nervous system, can be packed into EVs and transported to the periphery into easily obtainable biological specimens like blood, urine, and saliva. We performed a systematic review and meta-analysis of articles (published before November 15, 2022) reporting biomarker assessment in EVs in PD patients and healthy controls (HCs). Biomarkers were analyzed using random effects meta-analysis and the calculated standardized mean difference (Std.MD). Several proteins and ribonucleic acids have been identified in EVs in PD patients, but only α-synuclein (aSyn) and leucine-rich repeat kinase 2 (LRRK2) were reported in sufficient studies (n = 24 and 6, respectively) to perform a meta-analysis. EV aSyn was significantly increased in neuronal L1 cell adhesion molecule (L1CAM)-positive blood EVs in PD patients compared to HCs (Std.MD = 1.84, 95% confidence interval = 0.76-2.93, P = 0.0009). Further analysis of the biological sample and EV isolation method indicated that L1CAM-IP (immunoprecipitation) directly from plasma was the best isolation method for assessing aSyn in PD patients. Upcoming neuroprotective clinical trials immediately need peripheral biomarkers for identifying individuals at risk of developing PD. Overall, the improved sensitivity of assays means they can identify biomarkers in blood that reflect changes in the brain. CNS-derived EVs in blood will likely play a major role in biomarker development in the coming years. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
帕金森病（PD）的生物标志物是临床医生和研究人员都需要的（用于诊断、确定研究人群和监测治疗反应）。成像、遗传和生化生物标志物已得到广泛研究。近年来，细胞外囊泡（EVs）已成为生物标志物开发的有前途的材料。来自任何器官的蛋白质和分子物质，包括中枢神经系统，都可以被包装到 EVs 中，并运输到外周，进入血液、尿液和唾液等容易获得的生物样本中。我们对（截至 2022 年 11 月 15 日之前发表的）报告 PD 患者和健康对照者（HCs）中 EVs 中生物标志物评估的文章进行了系统评价和荟萃分析。使用随机效应荟萃分析和计算的标准化均数差（Std.MD）分析生物标志物。已经在 PD 患者的 EVs 中鉴定出几种蛋白质和核糖核酸，但只有α-突触核蛋白（aSyn）和富含亮氨酸重复激酶 2（LRRK2）在足够的研究（n = 24 和 6）中被报道以进行荟萃分析。与 HCs 相比，PD 患者神经元 L1 细胞黏附分子（L1CAM）阳性血 EVs 中的 EV aSyn 显著增加（Std.MD = 1.84，95%置信区间= 0.76-2.93，P = 0.0009）。对生物样本和 EV 分离方法的进一步分析表明，L1CAM-IP（免疫沉淀）直接从血浆中分离是评估 PD 患者 aSyn 的最佳分离方法。即将进行的神经保护临床试验立即需要外周生物标志物来识别有发展为 PD 风险的个体。总体而言，检测方法的灵敏度提高意味着它们可以识别反映大脑变化的血液中的生物标志物。未来几年，源自中枢神经系统的 EVs 在血液中的作用可能会在生物标志物开发中发挥重要作用。© 2023 作者。运动障碍由 Wiley 期刊代表国际帕金森病和运动障碍学会出版。
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