Soluble <scp>CD163</scp> Changes Indicate Monocyte Association With Cognitive Deficits in Parkinson's Disease

Nissen, Sara Konstantin; Ferreira, Sara; Nielsen, Marlene Christina; Schulte, Claudia; Shrivastava, Kalpana; Hennig, Dorle; Etzerodt, Anders; Graversen, Jonas Heilskov; Berg, Daniela; Maetzler, Walter; Panhelainen, Anne; Møller, Holger Jon; Brockmann, Kathrin; Romero‐Ramos, Marina

doi:10.1002/mds.28424

Cited by 45 publications

(55 citation statements)

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“…Furthermore, the iMos’ MFI of CD11b and CCR2 (females only) was higher in those patients with a MoCA scores indicative of cognitive impairment (MoCA ≤26). This corroborates that Mos with migratory capacity are associated with cognitive decline in PwP (Nissen et al, 2021; Umehara et al, 2020; Wijeyekoon et al, 2020b). Therefore, indicating that a long-term Mo dysregulation is disadvantageous for the patients, which deserves further investigation in a cohort with severe cognitive impairment.…”

Section: Discussionsupporting

confidence: 87%

“…CD163 is a MNP specific protein whose cleavage from the membrane surface is associated with Mo activation and production of sCD163 (Moller, 2012). We have previously shown that PwP’s blood immune cells in vitro have reduced ability to downregulate CD163 expression on CD14 + Mos upon exposure to α-syn (Nissen et al, 2019); and that PwP have increased sCD163 levels in serum (females only) and in CSF (both sexes), with CSF sCD163 levels associated with α-syn and cognitive deficits (Nissen et al, 2021). This data suggested a role for CD163 + cells in PD, thus we here analyzed the CD163 expression on MNPs.…”

Section: Resultsmentioning

confidence: 99%

“…Interestingly, the presentation of PD differs between sexes (Iwaki et al, 2021), with cognitive impairment being less likely to occur in female patients. We have previously reported a sex dimorphism in the CD163 related immune changes in serum from PwP (Nissen et al, 2021). In addition, it has recently been shown by transcriptomic analysis of blood CD14 + Mos that female with PD show a homogenous monocytic response while the response was more heterogenous in males (Carlisle et al, 2021).…”

Section: Introductionmentioning

confidence: 93%

“…We have previously shown that soluble (s)CD163, a marker produced upon activation of CD163-expressing MNPs, was increased in PD biofluids (Nissen et al, 2021). This elevation was related to PD-stages, defined by the disease duration, and associated with cognition and neuronal disease biomarkers such as α-syn and Tau.…”

Section: Introductionmentioning

confidence: 99%

“…Immune changes in the brain (Edison et al, 2013) associated with MNPs are suggested to be highly relevant in PwP with significant cognitive decline (Nissen et al, 2021; Wijeyekoon et al, 2020a). Interestingly, the presentation of PD differs between sexes (Iwaki et al, 2021), with cognitive impairment being less likely to occur in female patients.…”

Section: Introductionmentioning

confidence: 99%

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Changes in CD163+, CD11b+, and CCR2+ peripheral monocytes relate to Parkinson’s disease and cognition

Nissen¹,

Farmen²,

Gjelstrup³

et al. 2021

Preprint

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Background: Alpha-synuclein aggregates and accumulation are associated with immune activation and neurodegeneration in Parkinson's disease. The immune activation is not only dependent on the brain-resident microglial cells but also involves peripheral immune cells, such as mononuclear phagocytes including monocytes and dendritic cells, found in the blood as well as infiltrated into the brain. Understanding the involvement of the peripheral immune component in Parkinson's disease is essential for the development of immunomodulatory treatment, which might modify disease progression. We aimed to study the profile of circulating mononuclear phagocytes in early- and late-stage Parkinson's disease by analyzing surface-expressed molecules related to phagocytosis, alpha-synuclein sensing, and tissue-migration. Methods: Multi-color flow cytometry on peripheral mononuclear cells from cross-sectional samples of 80 gender-balance individuals with early- and late-stage sporadic Parkinson's disease, and 29 controls, as well as longitudinal samples from seven patients and one control. Cells were delineated into natural killer cells, monocyte subtypes, and dendritic cells with cell frequencies and surface marker expressions compared between patients and controls, and correlated with standardized clinical motor and non-motor scores. Results: Overall, we found elevated frequencies and surface levels of markers related to migration (CCR2, CD11b) and phagocytosis (CD163) particularly on the elevated classical and intermediate monocytes in patients with Parkinson's disease for less than five years. This corresponded to a decrease of non-classical monocytes and dendritic cells. We observed an increased HLA-DR expression late in disease and sexual-dimorphism with TLR-4 expression decreased in women with PD but not in males. The disease-associated immune changes on TLR4, CCR2, and CD11b were correlated with non-motor symptoms such as olfaction or cognition. While many alterations were normalized at late disease stage, other changes remained, such as the increased HLA-DR and CD163 expressions. Conclusions: Our data highlight a role for peripheral CD163+ and migration-competent classical monocytes in Parkinson's disease. The study further suggests that the peripheral immune system is dynamically altered in Parkinson's disease stages and directly related to both non-motor symptoms and the sex-bias of the disease.

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Section: Discussionsupporting

confidence: 87%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Changes in CD163+, CD11b+, and CCR2+ peripheral monocytes relate to Parkinson’s disease and cognition

Nissen¹,

Farmen²,

Gjelstrup³

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

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Dopaminergic regulation of inflammation and immunity in Parkinson's disease: friend or foe?

Furgiuele,

Pereira,

Martini

et al. 2023

Clin & Trans Imm

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Parkinson's disease (PD) is a neurodegenerative disease affecting 7–10 million people worldwide. Currently, there is no treatment available to prevent or delay PD progression, partially due to the limited understanding of the pathological events which lead to the death of dopaminergic neurons in the substantia nigra in the brain, which is known to be the cause of PD symptoms. The current available treatments aim at compensating dopamine (DA) deficiency in the brain using its precursor levodopa, dopaminergic agonists and some indirect dopaminergic agents. The immune system is emerging as a critical player in PD. Therefore, immune‐based approaches have recently been proposed to be used as potential antiparkinsonian agents. It has been well‐known that dopaminergic pathways play a significant role in regulating immune responses in the brain. Although dopaminergic agents are the primary antiparkinsonian treatments, their immune regulatory effect has yet to be fully understood. The present review summarises the current available evidence of the immune regulatory effects of DA and its mimics and discusses dopaminergic agents as antiparkinsonian drugs. Based on the current understanding of their involvement in the regulation of neuroinflammation in PD, we propose that targeting immune pathways involved in PD pathology could offer a better treatment outcome for PD patients.

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Shared Genetic Architecture between Parkinson's Disease and Brain Structural Phenotypes

Ma,

Li,

Shi

et al. 2023

Movement Disorders

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BackgroundPatients with Parkinson's disease (PD) have consistently demonstrated brain structure abnormalities, indicating the presence of shared etiological and pathological processes between PD and brain structures; however, the genetic relationship remains poorly understood.ObjectiveThe aim of this study was to investigate the extent of shared genetic architecture between PD and brain structural phenotypes (BSPs) and to identify shared genomic loci.MethodsWe used the summary statistics from genome‐wide association studies to conduct MiXeR and conditional/conjunctional false discovery rate analyses to investigate the shared genetic signatures between PD and BSPs. Subsequent expression quantitative trait loci mapping in the human brain and enrichment analyses were also performed.ResultsMiXeR analysis identified genetic overlap between PD and various BSPs, including total cortical surface area, average cortical thickness, and specific brain volumetric structures. Further analysis using conditional false discovery rate (FDR) identified 21 novel PD risk loci on associations with BSPs at conditional FDR < 0.01, and the conjunctional FDR analysis demonstrated that PD shared several genomic loci with certain BSPs at conjunctional FDR < 0.05. Among the shared loci, 16 credible mapped genes showed high expression in the brain tissues and were primarily associated with immune function–related biological processes.ConclusionsWe confirmed the polygenic overlap with mixed directions of allelic effects between PD and BSPs and identified multiple shared genomic loci and risk genes, which are likely related to immune‐related biological processes. These findings provide insight into the complex genetic architecture associated with PD. © 2023 International Parkinson and Movement Disorder Society.

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

Cited by 45 publications

References 76 publications

Changes in CD163+, CD11b+, and CCR2+ peripheral monocytes relate to Parkinson’s disease and cognition

Changes in CD163+, CD11b+, and CCR2+ peripheral monocytes relate to Parkinson’s disease and cognition

Dopaminergic regulation of inflammation and immunity in Parkinson's disease: friend or foe?

Shared Genetic Architecture between Parkinson's Disease and Brain Structural Phenotypes

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