外周炎症与帕金森病中的多巴胺能神经元变性有关。

Peripheral Inflammation Is Associated with Dopaminergic Degeneration in Parkinson's Disease.

机构信息

Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain.

Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.

出版信息

Mov Disord. 2023 May;38(5):755-763. doi: 10.1002/mds.29369. Epub 2023 Mar 13.

DOI:10.1002/mds.29369

PMID:36912400

Abstract

BACKGROUND

Peripheral inflammatory immune responses are suggested to play a major role in dopaminergic degeneration in Parkinson's disease (PD). The neutrophil-to-lymphocyte ratio (NLR) is a well-established biomarker of systemic inflammation in PD. Degeneration of the nigrostriatal dopaminergic system can be assessed in vivo using [ I]FP-CIT single photon emission computed tomography imaging of striatal dopamine transporter (DAT) density.

OBJECTIVES

To assess the relationship between the peripheral immune profile (NLR, lymphocytes, and neutrophils) and striatal DAT density in patients with PD.

METHODS

We assessed clinical features, the peripheral immune profile, and striatal [ I]FP-CIT DAT binding levels of 211 patients with PD (primary-cohort). Covariate-controlled associations between the immune response and striatal DAT levels were assessed using linear regression analyses. For replication purposes, we also studied a separate cohort of 344 de novo patients with PD enrolled in the Parkinson's Progression Markers Initiative (PPMI-cohort).

RESULTS

A higher NLR was significantly associated with lower DAT levels in the caudate (primary-cohort: β = -0.01, p < 0.001; PPMI-cohort: β = -0.05, p = 0.05) and the putamen (primary-cohort: β = -0.05, p = 0.02; PPMI-cohort: β = -0.06, p = 0.02). Intriguingly, a lower lymphocyte count was significantly associated with lower DAT levels in both the caudate (primary-cohort: β = +0.09, p < 0.05; PPMI-cohort: β = +0.11, p = 0.02) and the putamen (primary-cohort: β = +0.09, p < 0.05, PPMI-cohort: β = +0.14, p = 0.01), but an association with the neutrophil count was not consistently observed (caudate; primary-cohort: β = -0.05, p = 0.02; PPMI-cohort: β = 0, p = 0.94; putamen; primary-cohort: β = -0.04, p = 0.08; PPMI-cohort: β = -0.01, p = 0.73).

CONCLUSIONS

Our findings across two independent cohorts suggest a relationship between systemic inflammation and dopaminergic degeneration in patients with PD. This relationship was mainly driven by the lymphocyte count. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

摘要

背景

外周炎症免疫反应被认为在帕金森病（PD）中的多巴胺能变性中起主要作用。中性粒细胞与淋巴细胞比值（NLR）是 PD 中全身炎症的一种既定生物标志物。黑质纹状体多巴胺能系统的退化可以通过使用[I] FP-CIT 单光子发射计算机断层扫描成像来评估纹状体多巴胺转运体（DAT）密度。

目的

评估 PD 患者外周免疫特征（NLR、淋巴细胞和中性粒细胞）与纹状体 DAT 密度之间的关系。

方法

我们评估了 211 名 PD 患者（主要队列）的临床特征、外周免疫特征和纹状体[I] FP-CIT DAT 结合水平。使用线性回归分析评估免疫反应与纹状体 DAT 水平之间的协变量控制关联。为了复制目的，我们还研究了在帕金森病进展标志物倡议（PPMI 队列）中招募的 344 名新诊断的 PD 患者的独立队列。

结果

较高的 NLR 与尾状核（主要队列：β=-0.01，p<0.001；PPMI 队列：β=-0.05，p=0.05）和壳核（主要队列：β=-0.05，p=0.02；PPMI 队列：β=-0.06，p=0.02）的 DAT 水平显著相关。有趣的是，较低的淋巴细胞计数与尾状核（主要队列：β=+0.09，p<0.05；PPMI 队列：β=+0.11，p=0.02）和壳核（主要队列：β=+0.09，p<0.05，PPMI 队列：β=+0.14，p=0.01）的 DAT 水平显著相关，但与中性粒细胞计数的关联并不一致（尾状核；主要队列：β=-0.05，p=0.02；PPMI 队列：β=0，p=0.94；壳核；主要队列：β=-0.04，p=0.08；PPMI 队列：β=-0.01，p=0.73）。