炎症生物标志物在新发帕金森病及相关神经退行性疾病患者中的研究进展。
Inflammatory Biomarkers in Newly Diagnosed Patients With Parkinson Disease and Related Neurodegenerative Disorders.
机构信息
From the The Norwegian Centre for Movement Disorders (C.C.P., G.A., J.L., J.M.-G.), Stavanger University Hospital; Department of Chemistry, Bioscience and Environmental Engineering (C.C.P., G.A., J.L., J.M.-G.), University of Stavanger; Section of Biostatistics (A.U.), Department of Research, Stavanger University Hospital; Department of Geriatric Medicine (R.E.S.), Haraldsplass Deaconess Hospital, Bergen; Department of Clinical Medicine (R.E.S., O.-B.T.), University of Bergen; Department of Neurology (G.A.), Stavanger University Hospital; Department of Neurology (O.-B.T.), Haukeland University Hospital, Bergen; Centre for Age-Related Medicine (D.A.), Stavanger University Hospital, Norway; and Department of Old Age Psychiatry (D.A.), Institute of Psychiatry, Psychology, and Neuroscience, King's College London, United Kingdom.
出版信息
Neurol Neuroimmunol Neuroinflamm. 2023 May 31;10(4). doi: 10.1212/NXI.0000000000200132. Print 2023 Jul.
BACKGROUND AND OBJECTIVES
Neuroinflammation contributes to Parkinson disease (PD) pathology, and inflammatory biomarkers may aid in PD diagnosis. Proximity extension assay (PEA) technology is a promising method for multiplex analysis of inflammatory markers. Neuroinflammation also plays a role in related neurodegenerative diseases, such as dementia with Lewy bodies (DLB) and Alzheimer disease (AD). The aim of this work was to assess the value of inflammatory biomarkers in newly diagnosed patients with PD and in patients with DLB and AD.
METHODS
Patients from the Norwegian ParkWest and Dementia Study of Western Norway longitudinal cohorts (PD, n = 120; DLB, n = 15; AD, n = 27) and 44 normal controls were included in this study. A PEA inflammation panel of 92 biomarkers was measured in the CSF. Disease-associated biomarkers were identified using elastic net (EN) analysis. We assessed the discriminatory power of disease-associated biomarkers using receiver operating characteristic (ROC) curve analysis and estimated the optimism-adjusted area under the curve (AUC) using the bootstrapping method.
RESULTS
EN analysis identified 9 PEA inflammatory biomarkers (ADA, CCL23, CD5, CD8A, CDCP1, FGF-19, IL-18R1, IL-6, and MCP-2) associated with PD. Seven of the 9 biomarkers were included in a diagnostic panel, which was able to discriminate between those with PD and controls (optimism-adjusted AUC 0.82). Our 7-biomarker PD panel was also able to distinguish PD from DLB and from AD. In addition, 4 inflammatory biomarkers were associated with AD and included in a panel, which could distinguish those with AD from controls (optimism-adjusted AUC 0.87). Our 4-biomarker AD panel was also able to distinguish AD from DLB and from PD.
DISCUSSION
In our exploratory study, we identified a 7-biomarker panel for PD and a 4-biomarker panel for AD. Our findings indicate potential inflammation-related biomarker candidates that could contribute toward PD-specific and AD-specific diagnostic panels, which should be further explored in other larger cohorts.
背景与目的
神经炎症是帕金森病（PD）发病机制的一个重要因素，炎症生物标志物可能有助于 PD 的诊断。邻近延伸分析（PEA）技术是一种用于炎症标志物多重分析的很有前途的方法。神经炎症在其他相关神经退行性疾病中也发挥作用，如路易体痴呆（DLB）和阿尔茨海默病（AD）。本研究旨在评估炎症生物标志物在新诊断的 PD 患者以及 DLB 和 AD 患者中的价值。
方法
纳入挪威 ParkWest 和 Western Norway 纵向队列的痴呆研究（PD，n=120；DLB，n=15；AD，n=27）的患者以及 44 名正常对照者。使用 PEA 炎症面板检测了 92 种生物标志物。采用弹性网（EN）分析确定与疾病相关的生物标志物。我们使用受试者工作特征（ROC）曲线分析评估与疾病相关的生物标志物的判别能力，并使用自举法估计调整后的曲线下面积（AUC）。
结果
EN 分析确定了 9 个与 PD 相关的 PEA 炎症生物标志物（ADA、CCL23、CD5、CD8A、CDCP1、FGF-19、IL-18R1、IL-6 和 MCP-2）。这 9 个生物标志物中有 7 个被纳入一个诊断性面板，该面板能够区分 PD 患者和对照组（调整后的 AUC 为 0.82）。我们的 7 个生物标志物 PD 面板也能够区分 PD 与 DLB 和 AD。此外，有 4 个炎症生物标志物与 AD 相关，并被纳入一个能够区分 AD 患者与对照组的面板（调整后的 AUC 为 0.87）。我们的 4 个生物标志物 AD 面板也能够区分 AD 与 DLB 和 PD。
讨论
在我们的探索性研究中，我们确定了一个用于 PD 的 7 个生物标志物面板和一个用于 AD 的 4 个生物标志物面板。我们的研究结果表明，一些炎症相关的生物标志物候选物可能有助于开发 PD 特异性和 AD 特异性诊断面板，这需要在其他更大的队列中进一步探索。
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