Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Nissen SK

PROVIDER: S-EPMC8247308 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Context: Cognitive impairments are common in patients with Parkinson's disease (PD) and are heterogeneous in their presentation. The "dual syndrome hypothesis" suggests the existence of two distinct subtypes of mild cognitive impairment (MCI) in PD: a frontostriatal subtype with predominant attentional and/or executive deficits and a posterior cortical subtype with predominant visuospatial, memory, and/or language deficits. The latter subtype has been associated with a higher risk of developing dementia. Objective: The objective of this study was to identify structural modifications in cortical and subcortical regions associated with each PD-MCI subtype. Methods: One-hundred and fourteen non-demented PD patients underwent a comprehensive neuropsychological assessment as well as a 3T magnetic resonance imaging scan. Patients were categorized as having no cognitive impairment (n = 41) or as having a frontostriatal (n = 16), posterior cortical (n = 25), or a mixed (n = 32) MCI subtype. Cortical regions were analyzed using a surface-based Cortical thickness (CTh) method. In addition, the volumes, shapes, and textures of the caudate nuclei, hippocampi, and thalami were studied. Tractometric analyses were performed on associative and commissural white matter (WM) tracts. Results: There were no between-group differences in volumetric measurements and cortical thickness. Shape analyses revealed more abundant and more extensive deformations fields in the caudate nuclei, hippocampi, and thalami in patients with posterior cortical deficits compared to patients with no cognitive impairment. Decreased fractional anisotropy (FA) and increased mean diffusivity (MD) were also observed in the superior longitudinal fascicle, the inferior fronto-occipital fascicle, the striato-parietal tract, and the anterior and posterior commissural tracts. Texture analyses showed a significant difference in the right hippocampus of patients with a mixed MCI subtype. Conclusion: PD-MCI patients with posterior cortical deficits have more abundant and more extensive structural alterations independently of age, disease duration, and severity, which may explain why they have an increased risk of dementia.