Brain microglia activation and peripheral adaptive immunity in Parkinson’s disease: a multimodal PET study
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 activati...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2022-08-01
|
| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12974-022-02574-z |
| _version_ | 1817986641647632384 |
|---|---|
| author | Shu-Ying Liu Hong-Wen Qiao Tian-Bin Song Xiu-Lin Liu Yun-Xia Yao Chun-Song Zhao Olivier Barret Sheng-Li Xu Yan-Ning Cai Gilles D. Tamagnan Vesna Sossi Jie Lu Piu Chan |
| author_facet | Shu-Ying Liu Hong-Wen Qiao Tian-Bin Song Xiu-Lin Liu Yun-Xia Yao Chun-Song Zhao Olivier Barret Sheng-Li Xu Yan-Ning Cai Gilles D. Tamagnan Vesna Sossi Jie Lu Piu Chan |
| author_sort | Shu-Ying Liu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-14T00:11:48Z |
| format | Article |
| id | doaj.art-c609bd1c3e0b4251b727768e1d66d36a |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-04-14T00:11:48Z |
| publishDate | 2022-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-c609bd1c3e0b4251b727768e1d66d36a2022-12-22T02:23:19ZengBMCJournal of Neuroinflammation1742-20942022-08-011911910.1186/s12974-022-02574-zBrain microglia activation and peripheral adaptive immunity in Parkinson’s disease: a multimodal PET studyShu-Ying Liu0Hong-Wen Qiao1Tian-Bin Song2Xiu-Lin Liu3Yun-Xia Yao4Chun-Song Zhao5Olivier Barret6Sheng-Li Xu7Yan-Ning Cai8Gilles D. Tamagnan9Vesna Sossi10Jie Lu11Piu Chan12Department of Neurology, Xuanwu Hospital, Capital Medical UniversityDepartment of Radiology and Nuclear Medicine, Xuanwu Hospital, Capital Medical UniversityDepartment of Radiology and Nuclear Medicine, Xuanwu Hospital, Capital Medical UniversityDepartment of Neurology, Xuanwu Hospital, Capital Medical UniversityDepartment of Neurobiology, Xuanwu Hospital, Capital Medical UniversityDepartment of Neurobiology, Xuanwu Hospital, Capital Medical UniversityLaboratoire des Maladies Neurodégénératives, Université Paris-Saclay, CEA, CNRS, MIRCenDepartment of Neurobiology, Xuanwu Hospital, Capital Medical UniversityDepartment of Neurobiology, Xuanwu Hospital, Capital Medical UniversityNational Clinical Research Center for Geriatric DiseasesDepartment of Physics and Astronomy, University of British ColumbiaDepartment of Radiology and Nuclear Medicine, Xuanwu Hospital, Capital Medical UniversityDepartment of Neurology, Xuanwu Hospital, Capital Medical UniversityAbstract 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.https://doi.org/10.1186/s12974-022-02574-zParkinson’s diseaseMicrogliaCytokineTh cellLymphocytePositron emission tomograph |
| spellingShingle | Shu-Ying Liu Hong-Wen Qiao Tian-Bin Song Xiu-Lin Liu Yun-Xia Yao Chun-Song Zhao Olivier Barret Sheng-Li Xu Yan-Ning Cai Gilles D. Tamagnan Vesna Sossi Jie Lu Piu Chan Brain microglia activation and peripheral adaptive immunity in Parkinson’s disease: a multimodal PET study Journal of Neuroinflammation Parkinson’s disease Microglia Cytokine Th cell Lymphocyte Positron emission tomograph |
| title | Brain microglia activation and peripheral adaptive immunity in Parkinson’s disease: a multimodal PET study |
| title_full | Brain microglia activation and peripheral adaptive immunity in Parkinson’s disease: a multimodal PET study |
| title_fullStr | Brain microglia activation and peripheral adaptive immunity in Parkinson’s disease: a multimodal PET study |
| title_full_unstemmed | Brain microglia activation and peripheral adaptive immunity in Parkinson’s disease: a multimodal PET study |
| title_short | Brain microglia activation and peripheral adaptive immunity in Parkinson’s disease: a multimodal PET study |
| title_sort | brain microglia activation and peripheral adaptive immunity in parkinson s disease a multimodal pet study |
| topic | Parkinson’s disease Microglia Cytokine Th cell Lymphocyte Positron emission tomograph |
| url | https://doi.org/10.1186/s12974-022-02574-z |
| work_keys_str_mv | AT shuyingliu brainmicrogliaactivationandperipheraladaptiveimmunityinparkinsonsdiseaseamultimodalpetstudy AT hongwenqiao brainmicrogliaactivationandperipheraladaptiveimmunityinparkinsonsdiseaseamultimodalpetstudy AT tianbinsong brainmicrogliaactivationandperipheraladaptiveimmunityinparkinsonsdiseaseamultimodalpetstudy AT xiulinliu brainmicrogliaactivationandperipheraladaptiveimmunityinparkinsonsdiseaseamultimodalpetstudy AT yunxiayao brainmicrogliaactivationandperipheraladaptiveimmunityinparkinsonsdiseaseamultimodalpetstudy AT chunsongzhao brainmicrogliaactivationandperipheraladaptiveimmunityinparkinsonsdiseaseamultimodalpetstudy AT olivierbarret brainmicrogliaactivationandperipheraladaptiveimmunityinparkinsonsdiseaseamultimodalpetstudy AT shenglixu brainmicrogliaactivationandperipheraladaptiveimmunityinparkinsonsdiseaseamultimodalpetstudy AT yanningcai brainmicrogliaactivationandperipheraladaptiveimmunityinparkinsonsdiseaseamultimodalpetstudy AT gillesdtamagnan brainmicrogliaactivationandperipheraladaptiveimmunityinparkinsonsdiseaseamultimodalpetstudy AT vesnasossi brainmicrogliaactivationandperipheraladaptiveimmunityinparkinsonsdiseaseamultimodalpetstudy AT jielu brainmicrogliaactivationandperipheraladaptiveimmunityinparkinsonsdiseaseamultimodalpetstudy AT piuchan brainmicrogliaactivationandperipheraladaptiveimmunityinparkinsonsdiseaseamultimodalpetstudy |