Background: Parkinson's disease (PD) is a neurodegenerative disorder with a significant immune component, as demonstrated by changes in immune biomarkers in patients' biofluids. However, which specific cells are responsible for those changes is unclear since most immune biomarkers can be produced by various cell types. Objectives and methods: To explore monocyte involvement in PD, we investigated the monocyte-specific biomarker sCD163, the soluble form of the receptor CD163, in cerebrospinal fluid (CSF) and serum in two experiments, and compared it with other biomarkers and clinical data. Potential connections between CD163 and alpha-synuclein were studied in vitro. Results: CSF-sCD163 increased in late-stage PD and correlated with the PD biomarkers alpha-synuclein, Tau, and phosphorylated Tau, while it inversely correlated with the patients' cognitive scores, supporting monocyte involvement in neurodegeneration and cognition in PD. Serum-sCD163 only increased in female patients, suggesting a sex-distinctive monocyte response. CSF-sCD163 also correlated with molecules associated with adaptive and innate immune system activation and with immune cell recruitment to the brain. Serum-sCD163 correlated with pro-inflammatory cytokines and acute phase proteins, suggesting a relation to chronic systemic inflammation. Our in vitro study showed that alpha-synuclein activates macrophages and induces shedding of sCD163, which in turn enhances alpha-synuclein uptake by myeloid cells, potentially participating in its clearance. Conclusion: Our data present sCD163 as a potential cognition-related biomarker in PD and suggest a role for monocytes both in peripheral and brain immune responses. This may be directly related to alpha-synuclein's pro-inflammatory capacity but could also have consequences for alpha-synuclein processing.

中文翻译：

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可溶性CD163改变表明单核细胞与帕金森氏病认知障碍相关

背景：帕金森氏病（PD）是一种具有重要免疫成分的神经退行性疾病，患者生物流体中免疫生物标志物的变化证明了这一点。但是，尚不清楚哪些特定细胞负责这些变化，因为大多数免疫生物标记物可以由多种细胞类型产生。目的和方法：为了研究单核细胞参与PD，我们在两个实验中研究了单核细胞特异性生物标志物sCD163（CD163受体的可溶形式）在脑脊髓液（CSF）和血清中的表达，并将其与其他生物标志物和临床数据进行了比较。体外研究了CD163和α-突触核蛋白之间的潜在联系。结果：CSF-sCD163在晚期PD中升高，并与PD生物标志物α-突触核蛋白，Tau和磷酸化Tau相关，而它与患者的认知评分呈负相关，支持单核细胞参与PD的神经变性和认知。血清-sCD163仅在女性患者中增加，表明性别区分性单核细胞反应。CSF-sCD163还与与适应性和先天性免疫系统激活以及与免疫细胞募集到大脑有关的分子有关。血清-sCD163与促炎细胞因子和急性期蛋白相关，提示与慢性全身性炎症有关。我们的体外研究表明，α-突触核蛋白可激活巨噬细胞并诱导sCD163脱落，进而增强髓样细胞对α-突触核蛋白的吸收，可能参与其清除。结论：我们的数据显示sCD163是PD中潜在的认知相关生物标志物，并提示单核细胞在外周和脑部免疫反应中均发挥作用。这可能与α-突触核蛋白的促炎能力直接相关，但也可能对α-突触核蛋白的加工产生影响。