Nigral Neuroinflammation and Dopaminergic Neurons in Parkinson's Disease and Atypical Parkinsonisms

IF 7.7 1区医学 Q1 CLINICAL NEUROLOGY Annals of Neurology Pub Date : 2025-02-07 DOI:10.1002/ana.27202

Emmilotta A. Backman BM, Maria Gardberg MD, PhD, Laura Luntamo MD, PhD, Markus Peurla PhD, Tero Vahlberg MSc, Per Borghammer MD, PhD, Nadia Stefanova MD, PhD, Gregor Wenning MD, PhD, Valtteri Kaasinen MD, PhD

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Abstract

Objective

To investigate the role of neuroinflammation in the substantia nigra pars compacta (SNc) across different parkinsonian disorders—Parkinson's disease (PD), progressive supranuclear palsy (PSP), and multiple system atrophy (MSA)—by examining SNc dopaminergic neuron counts, neuroinflammatory T cells, and microglial activity.

Methods

Postmortem neuropathological samples were collected from 79 individuals (PD, n = 38; PSP, n = 15; MSA, n = 14; controls, n = 12). The density of SNc tyrosine hydroxylase (TH)-positive neurons, T cells (CD3+, CD4+, and CD8+), and Iba1 expression (Iba1-positive microglia/macrophages) were examined in the SNc and crus cerebri. Demographic and clinical data were gathered from patient histories.

Results

PSP patients had 89 to 212% more nigral CD3+, CD4+, and CD8+ T cells compared to MSA patients (p < 0.04), 125 to 178% more CD3+ and CD4+ T cells than healthy controls (p < 0.002), and 95% more CD4+ T cells than PD patients (p = 0.001). Iba1 expression in the SNc was higher in PD patients than in MSA patients (p = 0.004), with no significant differences observed across other conditions. There was a negative association between disease duration and SNc CD3+ T cell density (p = 0.002), and a positive correlation between nigral dopaminergic neuron density and CD3+ density, CD8+ density, and Iba1 expression in PD patients.

Interpretation

The study reveals distinctive neuroinflammatory patterns in the SNc, with T cell-mediated inflammation prominent in PSP and microglia-mediated inflammation in PD. PSP and MSA show greater SNc dopaminergic neuron loss compared to PD. Increased neuroinflammatory response is seen in earlier disease stages, diminishing with greater neuron loss, which may inform disease progression understanding and therapeutic strategies. ANN NEUROL 2025;97:1096–1109

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帕金森病和非典型帕金森病的神经炎症和多巴胺能神经元。

目的：通过检测不同帕金森病——帕金森病（PD）、进行性核上性麻痹（PSP）和多系统萎缩（MSA）的黑质致密部（SNc）多巴胺能神经元计数、神经炎性T细胞和小胶质细胞活性，探讨神经炎症在SNc中的作用。方法：采集79例PD患者的死后神经病理标本(n = 38；PSP, n = 15；MSA, n = 14；对照组，n = 12)。检测SNc和脑小腿中酪氨酸羟化酶（TH）阳性神经元密度、T细胞（CD3+、CD4+和CD8+）和Iba1表达（Iba1阳性的小胶质细胞/巨噬细胞）。从患者病史中收集人口统计学和临床数据。结果：与MSA患者相比，PSP患者的黑质CD3+、CD4+和CD8+ T细胞比MSA患者多89 - 212%。(p)解释：研究揭示了SNc中独特的神经炎症模式，PSP中T细胞介导的炎症突出，PD中小胶质细胞介导的炎症突出。与PD相比，PSP和MSA显示更大的SNc多巴胺能神经元损失。在疾病早期可以看到神经炎症反应增加，随着神经元损失的增加而减弱，这可能为疾病进展的理解和治疗策略提供信息。Ann neurol 2025。

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来源期刊

Annals of Neurology 医学-临床神经学

CiteScore

18.00

自引率

1.80%

发文量

270

审稿时长

3-8 weeks

期刊介绍： Annals of Neurology publishes original articles with potential for high impact in understanding the pathogenesis, clinical and laboratory features, diagnosis, treatment, outcomes and science underlying diseases of the human nervous system. Articles should ideally be of broad interest to the academic neurological community rather than solely to subspecialists in a particular field. Studies involving experimental model system, including those in cell and organ cultures and animals, of direct translational relevance to the understanding of neurological disease are also encouraged.