Brain microglia activation and peripheral adaptive immunity in Parkinson's disease: a multimodal PET study - PubMed (original) (raw)

doi: 10.1186/s12974-022-02574-z.

Shu-Ying Liu # 1 2 3, Tian-Bin Song 4, Xiu-Lin Liu 6, Yun-Xia Yao 7, Chun-Song Zhao 7, Olivier Barret 8, Sheng-Li Xu 7, Yan-Ning Cai 7, Gilles D Tamagnan 5 9, Vesna Sossi 10, Jie Lu 4, Piu Chan 11 12

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

Shu-Ying Liu et al. J Neuroinflammation. 2022.

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.

Keywords: Cytokine; Lymphocyte; Microglia; Parkinson’s disease; Positron emission tomograph; Th cell.

© 2022. The Author(s).

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1

Fig. 1

Neuroinflammation in striatum subregions, substantia nigra and brainstem. The SUVR of 18F-PBR06 between patients with Parkinson’s disease and healthy controls in the A caudate, B putamen, C substantial nigra, D brainstem. _C_Contralateral side to the onset side of motor symptoms. I Ipsilateral side to the onset side of motor symptoms. PD Parkinson’s disease, SUVR standardized uptake value ratio

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References

    1. Bloem BR, Okun MS, Klein C. Parkinson’s disease. Lancet. 2021;397(10291):2284–2303. doi: 10.1016/S0140-6736(21)00218-X. - DOI - PubMed
    1. McGeer PL, Itagaki S, Boyes BE, McGeer EG. Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson’s and Alzheimer’s disease brains. Neurology. 1988;38(8):1285–1291. doi: 10.1212/WNL.38.8.1285. - DOI - PubMed
    1. Imamura K, Hishikawa N, Sawada M, Nagatsu T, Yoshida M, Hashizume Y. Distribution of major histocompatibility complex class II-positive microglia and cytokine profile of Parkinson’s disease brains. Acta Neuropathol. 2003;106(6):518–526. doi: 10.1007/s00401-003-0766-2. - DOI - PubMed
    1. Jiang S, Gao H, Luo Q, Wang P, Yang X. The correlation of lymphocyte subsets, natural killer cell, and Parkinson’s disease: a meta-analysis. Neurol Sci. 2017;38(8):1373–1380. doi: 10.1007/s10072-017-2988-4. - DOI - PubMed
    1. Qin XY, Zhang SP, Cao C, Loh YP, Cheng Y. Aberrations in peripheral inflammatory cytokine levels in Parkinson disease: a systematic review and meta-analysis. JAMA Neurol. 2016;73(11):1316–1324. doi: 10.1001/jamaneurol.2016.2742. - DOI - PubMed

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