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

被引：39

作者：

Nissen, Sara Konstantin ^{[1
,2
]}

Ferreira, Sara Almeida ^{[1
,2
]}

Nielsen, Marlene Christina ^{[3
]}

Schulte, Claudia ^{[4
,5
,6
]}

Shrivastava, Kalpana ^{[1
,2
]}

Hennig, Dorle ^{[7
]}

Etzerodt, Anders ^{[1
,2
]}

Graversen, Jonas Heilskov ^{[7
]}

Berg, Daniela ^{[4
,5
,6
,8
]}

Maetzler, Walter ^{[8
]}

Panhelainen, Anne ^{[9
]}

Moller, Holger Jon ^{[3
]}

Brockmann, Kathrin ^{[4
,5
,6
]}

Romero-Ramos, Marina ^{[1
,2
]}

机构：

[1] Aarhus Univ, DANDRITE, Aarhus, Denmark

[2] Aarhus Univ, Dept Biomed, Hoegh Guldbergsgade 10, DK-8000 Aarhus, Denmark

[3] Aarhus Univ Hosp, Dept Clin Biochem, Aarhus, Denmark

[4] Univ Tubingen, Dept Neurodegenerat, Ctr Neurol, Tubingen, Germany

[5] Univ Tubingen, Hertie Inst Clin Brain Res, Tubingen, Germany

[6] Univ Tubingen, German Ctr Neurodegenerat Dis, Tubingen, Germany

[7] Univ Southern Denmark, Dept Mol Med, Odense, Denmark

[8] Univ Kiel, Dept Neurol, Kiel, Germany

[9] Univ Helsinki, Inst Biotechnol, Helsinki, Finland

来源：

MOVEMENT DISORDERS | 2021年 / 36卷 / 04期

关键词：

alpha‐ synuclein; biomarkers; cognition; monocytes; sCD163; SCAVENGER RECEPTOR CD163; INFLAMMATORY PROFILE; ACTIVATION MARKER; T-TAU; MICROGLIA; IMMUNE; CELLS; INTERLEUKIN-15; IDENTIFICATION; POLARIZATION;

D O I：

10.1002/mds.28424

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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. (c) 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

引用

页码：963 / 976

页数：14

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