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Brain microglia activation and peripheral adaptive immunity in Parkinson's disease: a multimodal PET study

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机构: [1]Capital Med Univ, Xuanwu Hosp, Dept Neurol, Changchun St 45, Beijing 100053, Peoples R China [2]Capital Med Univ, Xuanwu Hosp, Dept Radiol & Nucl Med, Beijing, Peoples R China [3]Capital Med Univ, Xuanwu Hosp, Dept Neurobiol, Beijing, Peoples R China [4]Chinese Inst Brain Res CIBR, Beijing, Peoples R China [5]Univ Ris Saclay, Lab Malad Neurodegenerat, CNRS, CEA,MIRCen, Fontenay Aux Roses, France [6]Natl Clin Res Ctr Geriatr Dis, Beijing, Peoples R China [7]Yale Univ, Mental Hlth Pet Radioligand Dev MHPRD Program, New Haven, CT USA [8]Univ British Columbia, Dept Phys & Astron, Vancouver, BC, Canada
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关键词: Parkinson's disease Microglia Cytokine Th cell Lymphocyte Positron emission tomograph

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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. F-18-PBR06 PET/MR for microglia activation, F-18-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 F-18-PBR06-PET. Results Compared to healthy controls, patients with Parkinson's disease had an increased F-18-PBR06-PET standardized uptake value ratio (SUVR) in the putamen, particularly in the ipsilateral side of the motor onset. F-18-PBR06-PET SUVR was positively associated with F-18-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.

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出版当年[2021]版:
大类 | 1 区 医学
小类 | 1 区 免疫学 1 区 神经科学
最新[2023]版:
大类 | 1 区 医学
小类 | 1 区 免疫学 1 区 神经科学
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出版当年[2020]版:
Q1 IMMUNOLOGY Q1 NEUROSCIENCES
最新[2023]版:
Q1 NEUROSCIENCES Q1 IMMUNOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2020版] 出版当年五年平均 出版前一年[2019版] 出版后一年[2021版]

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第一作者机构: [1]Capital Med Univ, Xuanwu Hosp, Dept Neurol, Changchun St 45, Beijing 100053, Peoples R China [4]Chinese Inst Brain Res CIBR, Beijing, Peoples R China [6]Natl Clin Res Ctr Geriatr Dis, Beijing, Peoples R China
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通讯机构: [1]Capital Med Univ, Xuanwu Hosp, Dept Neurol, Changchun St 45, Beijing 100053, Peoples R China [4]Chinese Inst Brain Res CIBR, Beijing, Peoples R China [6]Natl Clin Res Ctr Geriatr Dis, Beijing, Peoples R China
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