Soluble CD163 Changes Indicate Monocyte Association With Cognitive Deficits in Parkinson's Disease

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 because most immune biomarkers can be produced by various cell types. OBJECTIVES: The aim of this study was to explore monocyte involvement in PD. METHODS: 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, whereas it inversely correlated with the patients' cognitive scores, supporting monocyte involvement in neurodegeneration and cognition in PD. Serum‐sCD163 increased only 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 proinflammatory 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. CONCLUSIONS: Our data present sCD163 as a potential cognition‐related biomarker in PD and suggest a role for monocytes in both peripheral and brain immune responses. This may be directly related to alpha‐synuclein's proinflammatory capacity but could also have consequences for alpha‐synuclein processing. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society