Research Imaging Centre, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada.
Krembil Research Institute, University Health Network (UHN), University of Toronto, Toronto, Ontario, Canada.
Mol Neurobiol. 2020 Jan;57(1):492-501. doi: 10.1007/s12035-019-01714-6. Epub 2019 Aug 5.
Activated microglia have been reported to play an important role in Parkinson's disease (PD). A more rapid cognitive decline has been associated with deposits of β-amyloid. In this study, the aim was to evaluate the role of brain β-amyloid and its relationship with activated microglia in PD patients with normal and impaired cognition. We studied 17 PD patients with normal cognition (PDn), 12 PD patients with mild cognitive impairment (PD-MCI), and 12 healthy controls (HCs) with [C] Pittsburgh compound B (PIB) to assess the impact of β-amyloid deposition in the brain on microglial activation evaluated using the translocator protein 18-kDa (TSPO) radioligand [F]-FEPPA. [C] PIB distribution volume ratio was measured in cortical and subcortical regions. [F]-FEPPA total distribution volume values were compared for each brain region between groups to evaluate the effect of PIB positivity while adjusting for the TSPO rs6971 polymorphism. Factorial analysis of variance revealed a significant main effect of PIB positivity in the frontal lobe (F = 7.1, p = 0.012). Besides the frontal (p = 0.006) and temporal lobe (p = 0.001), the striatum (p = 0.018), the precuneus (p = 0.019), and the dorsolateral prefrontal cortex (p = 0.010) showed significant group × PIB positivity interaction effects. In these regions, PD-MCIs had significantly higher FEPPA V if PIB-positive. Our results indicate an interaction between amyloid-β deposition and microglial activation in PD. Further investigations are necessary to evaluate if amyloid deposits cause neuroinflammation and further neurodegeneration or if increased microglia activation develops as a protective response.
已报道活化的小胶质细胞在帕金森病（PD）中发挥重要作用。β-淀粉样蛋白沉积与认知衰退速度加快有关。本研究旨在评估脑β-淀粉样蛋白及其与认知正常和受损的 PD 患者中活化小胶质细胞的关系。我们研究了 17 名认知正常的 PD 患者（PDn）、12 名轻度认知障碍的 PD 患者（PD-MCI）和 12 名健康对照者（HCs），采用[C]匹兹堡复合物 B（PIB）评估脑内β-淀粉样蛋白沉积对使用转位蛋白 18kDa（TSPO）放射性配体[F]-FEPPA 评估的小胶质细胞活化的影响。在皮质和皮质下区域测量[C] PIB 分布容积比。为了评估 PIB 阳性对 TSPO rs6971 多态性的影响，比较了每组脑区之间[F]-FEPPA 总分布容积值。方差因子分析显示额叶 PIB 阳性有显著的主效应（F=7.1，p=0.012）。除了额叶（p=0.006）和颞叶（p=0.001），纹状体（p=0.018）、楔前叶（p=0.019）和背外侧前额叶皮质（p=0.010）也显示出显著的组×PIB 阳性相互作用效应。在这些区域，PD-MCI 如果 PIB 阳性则[F]-FEPPA V 显著更高。我们的结果表明 PD 中存在淀粉样蛋白-β沉积与小胶质细胞活化的相互作用。需要进一步研究以评估淀粉样蛋白沉积是否导致神经炎症和进一步的神经退行性变，或者是否增加小胶质细胞活化作为一种保护反应而发生。
