Synucleinopathies are neurodegenerative diseases with both central and peripheral immune responses. However, whether the peripheral immune changes occur early in disease and their relation to brain events is yet unclear. Isolated rapid-eye-movement (REM) sleep behavior disorder (iRBD) can precede synucleinopathy-related parkinsonism and provides a prodromal phenotype to study early Parkinson's disease events. In this prospective case-control study, we describe monocytic markers in a cohort of iRBD patients that were associated with the brain-imaging markers of inflammation and neuronal dysfunction. Using ¹¹C-PK11195 positron emission tomography (PET), we previously showed increased immune activation in the substantia nigra of iRBD patients, while ¹⁸F-DOPA PET detected reduced putaminal dopaminergic function. Here we describe that patients’ blood monocytic cells showed increased expression of CD11b, while HLA-DR expression was decreased compared to healthy controls. The iRBD patients had increased classical monocytes and mature natural killer cells. Remarkably, the levels of expression of Toll-like receptor 4 (TLR4) on blood monocytes in iRBD patients were positively correlated with nigral immune activation measured by ¹¹C-PK11195 PET and negatively correlated with putaminal ¹⁸F-DOPA uptake; the opposite was seen for the percentage of CD163⁺ myeloid cells. This suggesting a deleterious role for TLR4 and, conversely, a protective one for the CD163 expression. We show an association between peripheral blood monocytes and brain immune and dopaminergic changes in a synucleinopathy-related disorder, thus suggesting a cross-talk among periphery and brain during the disease.

突触核蛋白病是具有中枢和外周免疫反应的神经退行性疾病。然而，外周免疫变化是否在疾病早期发生及其与大脑事件的关系尚不清楚。孤立的快速眼动 (REM) 睡眠行为障碍 (iRBD) 可以先于突触核蛋白病相关的帕金森病，并提供前驱表型来研究早期帕金森病事件。在这项前瞻性病例对照研究中，我们描述了一组 iRBD 患者中的单核细胞标志物，这些标志物与炎症和神经元功能障碍的脑成像标志物相关。使用¹¹ C-PK11195 正电子发射断层扫描 (PET)，我们之前显示 iRBD 患者黑质中的免疫激活增加，而¹⁸F-DOPA PET 检测到壳核多巴胺能功能降低。在这里，我们描述了患者的血液单核细胞显示出 CD11b 表达增加，而与健康对照相比，HLA-DR 表达降低。iRBD 患者的经典单核细胞和成熟的自然杀伤细胞增加。值得注意的是，iRBD患者血液单核细胞上Toll样受体4（TLR4）的表达水平与¹¹ C-PK11195 PET测量的黑质免疫激活呈正相关，与壳核¹⁸ F-DOPA摄取呈负相关；CD163 ⁺的百分比相反髓细胞。这表明 TLR4 具有有害作用，相反，它对 CD163 表达具有保护作用。我们显示了外周血单核细胞与突触核蛋白病相关疾病中脑免疫和多巴胺能变化之间的关联，从而表明疾病期间外周和大脑之间存在串扰。