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Inflammatory Biomarkers in Newly Diagnosed Patients With Parkinson Disease and Related Neurodegenerative Disorders
Neurology Neuroimmunology & Neuroinflammation ( IF 8.8 ) Pub Date : 2023-07-01 , DOI: 10.1212/nxi.0000000000200132
Camilla Christina Pedersen 1 , Anastasia Ushakova 1 , Ragnhild Eide Skogseth 1 , Guido Alves 1 , Ole-Bjørn Tysnes 1 , Dag Aarsland 1 , Johannes Lange 1 , Jodi Maple-Grødem 1
Affiliation  

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.



中文翻译:

新诊断的帕金森病和相关神经退行性疾病患者的炎症生物标志物

背景和目标

神经炎症有助于帕金森病 (PD) 病理学,炎症生物标志物可能有助于 PD 诊断。邻近延伸测定 (PEA) 技术是一种很有前途的炎症标志物多重分析方法。神经炎症还在相关的神经退行性疾病中发挥作用,例如路易体痴呆 (DLB) 和阿尔茨海默病 (AD)。这项工作的目的是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

来自挪威西部纵向队列的挪威 ParkWest 和痴呆研究的患者(PD,n = 120;DLB,n = 15;AD,n = 27)和 44 名正常对照被纳入本研究。在 CSF 中测量了 92 种生物标志物的 PEA 炎症组。使用弹性网 (EN) 分析确定疾病相关生物标志物。我们使用接受者操作特征 (ROC) 曲线分析评估了疾病相关生物标志物的辨别力,并使用 bootstrapping 方法估计了乐观调整的曲线下面积 (AUC)。

结果

EN 分析确定了 9 种与 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)。9 种生物标志物中的 7 种包含在诊断组中,能够区分 PD 患者和对照组(乐观调整后的 AUC 0.82)。我们的 7 生物标志物 PD 组合也能够将 PD 与 DLB 和 AD 区分开来。此外,4 种炎症生物标志物与 AD 相关并包含在一个组中,这可以将 AD 患者与对照组区分开来(乐观调整后的 AUC 0.87)。我们的 4 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 PD 的 7 种生物标志物组和 AD 的 4 种生物标志物组。我们的研究结果表明潜在的炎症相关生物标志物候选物可能有助于 PD 特异性和 AD 特异性诊断组,应在其他更大的队列中进一步探索。

更新日期:2023-06-01
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