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Brain microglia activation and peripheral adaptive immunity in Parkinson’s disease: a multimodal PET study Liu, Shu-Ying; Qiao, Hong-Wen; Song, Tian-Bin; Liu, Xiu-Lin; Yao, Yun-Xia; Zhao, Chun-Song; Barret, Olivier; Xu, Sheng-Li; Cai, Yan-Ning; Tamagnan, Gilles D.; Sossi, Vesna; Lu, Jie; Chan, Piu

Abstract

Background Abnormal activation of immune system is an important pathogenesis of Parkinson’s disease, but the relationship between peripheral inflammation, central microglia activation and dopaminergic degeneration remains unclear. Objectives To evaluate the brain regional microglia activation and its relationship with clinical severity, dopaminergic presynaptic function, and peripheral inflammatory biomarkers related to adaptive immunity. Methods In this case–control study, we recruited 23 healthy participants and 24 participants with early-stage Parkinson’s disease. 18F-PBR06 PET/MR for microglia activation, 18F-FP-DTBZ for dopaminergic denervation, total account of T cells and subpopulations of T helper (Th1/Th2/Th17) cells, and the levels of serum inflammatory cytokines were assessed. Sanger sequencing was used to exclude the mix-affinity binders of 18F-PBR06-PET. Results Compared to healthy controls, patients with Parkinson’s disease had an increased 18F-PBR06-PET standardized uptake value ratio (SUVR) in the putamen, particularly in the ipsilateral side of the motor onset. 18F-PBR06-PET SUVR was positively associated with 18F-FP-DTBZ-PET SUVR in the brainstem and not associated with disease severity measured by Hoehn and Yahr stage, MDS-UPDRS III scores. Patients with Parkinson’s disease had elevated frequencies of Th1 cells and serum levels of IL10 and IL17A as compared to healthy controls. No significant association between peripheral inflammation markers and microglia activation in the brain of PD was observed. Conclusion Parkinson’s disease is associated with early putaminal microglial activation and peripheral phenotypic Th1 bias. Peripheral adaptive immunity might be involved in microglia activation in the process of neurodegeneration in PD indirectly, which may be a potential biomarker for the early detection and the target for immunomodulating therapy.

Item Metadata

Title
Brain microglia activation and peripheral adaptive immunity in Parkinson’s disease: a multimodal PET study
Creator
Liu, Shu-Ying; Qiao, Hong-Wen; Song, Tian-Bin; Liu, Xiu-Lin; Yao, Yun-Xia; Zhao, Chun-Song; Barret, Olivier; Xu, Sheng-Li; Cai, Yan-Ning; Tamagnan, Gilles D.; Sossi, Vesna; Lu, Jie; Chan, Piu
Publisher
BioMed Central
Date Issued
2022-08-29
Description
Background Abnormal activation of immune system is an important pathogenesis of Parkinson’s disease, but the relationship between peripheral inflammation, central microglia activation and dopaminergic degeneration remains unclear. Objectives To evaluate the brain regional microglia activation and its relationship with clinical severity, dopaminergic presynaptic function, and peripheral inflammatory biomarkers related to adaptive immunity. Methods In this case–control study, we recruited 23 healthy participants and 24 participants with early-stage Parkinson’s disease. 18F-PBR06 PET/MR for microglia activation, 18F-FP-DTBZ for dopaminergic denervation, total account of T cells and subpopulations of T helper (Th1/Th2/Th17) cells, and the levels of serum inflammatory cytokines were assessed. Sanger sequencing was used to exclude the mix-affinity binders of 18F-PBR06-PET. Results Compared to healthy controls, patients with Parkinson’s disease had an increased 18F-PBR06-PET standardized uptake value ratio (SUVR) in the putamen, particularly in the ipsilateral side of the motor onset. 18F-PBR06-PET SUVR was positively associated with 18F-FP-DTBZ-PET SUVR in the brainstem and not associated with disease severity measured by Hoehn and Yahr stage, MDS-UPDRS III scores. Patients with Parkinson’s disease had elevated frequencies of Th1 cells and serum levels of IL10 and IL17A as compared to healthy controls. No significant association between peripheral inflammation markers and microglia activation in the brain of PD was observed. Conclusion Parkinson’s disease is associated with early putaminal microglial activation and peripheral phenotypic Th1 bias. Peripheral adaptive immunity might be involved in microglia activation in the process of neurodegeneration in PD indirectly, which may be a potential biomarker for the early detection and the target for immunomodulating therapy.
Subject
Parkinson’s disease; Microglia; Cytokine; Th cell; Lymphocyte; Positron emission tomograph
Genre
Article
Type
Text
Language
eng
Date Available
2023-05-01
Provider
Vancouver : University of British Columbia Library
Rights
Attribution 4.0 International (CC BY 4.0)
DOI
10.14288/1.0431518
URI
http://hdl.handle.net/2429/84527
Affiliation
Science, Faculty of; Non UBC; Physics and Astronomy, Department of
Citation
Journal of Neuroinflammation. 2022 Aug 29;19(1):209
Publisher DOI
10.1186/s12974-022-02574-z
Peer Review Status
Reviewed
Scholarly Level
Faculty; Researcher
Copyright Holder
The Author(s)
Rights URI
http://creativecommons.org/licenses/by/4.0/
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Attribution 4.0 International (CC BY 4.0)