Microglia, Amyloid, and Glucose Metabolism in Parkinson's Disease with and without Dementia
Microglia, Amyloid, and Glucose Metabolism in Parkinson's Disease with and without Dementia
复制标题
DOI：
10.1038/npp.2012.255
复制
发表时间：
2013-05-01
影响因子：
7.6
通讯作者：
Brooks, David J.
中科院分区：
文献类型：
--
作者：
Edison, Paul;Ahmed, Imtiaz;Brooks, David J.
[C-11](R)PK11195-PET测量与小胶质细胞激活相关的转位蛋白上调，[C-11]PIB-PET是淀粉样蛋白的标志，而[F-18]FDG-PET测量大脑葡萄糖代谢(RCMRGlc)。我们假设小胶质细胞的激活是帕金森病(PD)谱系中的早期事件，并且独立于淀粉样蛋白病理。本研究的目的是在体内评估帕金森病痴呆(PDD)和非痴呆PD患者的小胶质细胞激活、淀粉样蛋白沉积和糖代谢之间的关系。在这里，我们评估了11名PDD受试者，8名非痴呆症帕金森病受试者和24名对照受试者。受试者接受T1和T2磁共振、[C-11](R)PK11195、[F-18]FDG和[C-11]PIB PET扫描。[C-11](R)PK11195结合势、rCMRGlc和[C-11]PIB摄取的参数图使用感兴趣区和SPM(统计参数映射)分析。与对照组相比，PDD患者前部和后部扣带回、纹状体、额叶、颞叶、顶叶和枕叶皮质的小胶质细胞激活显著增加。帕金森病受试者在颞区、顶区和枕区的小胶质细胞激活也有统计学意义的增加。[C-11]PDD和PD的PIB摄取略有增加。PDD和PD患者的糖代谢显著降低。我们还证明了简易精神状态检查(MMSE)评分和小胶质细胞激活之间的逐个像素的相关性，以及MMSE评分和rCMRGlc之间的相关性。总而言之，我们已经证明，皮质小胶质细胞激活和糖代谢降低可以在这种疾病谱的早期被检测到。显著的小胶质细胞激活可能是推动PDD疾病进程的一个因素。有鉴于此，影响小胶质细胞激活的因素可能会对疾病的进展产生影响。《神经精神药理学》(2013年)38938-949；DOI：10.1038/npp.2012.255；2013年1月16日在线发布
[C-11](R)PK11195-PET measures upregulation of translocator protein, which is associated with microglial activation, [C-11]PIB-PET is a marker of amyloid, while [F-18]FDG-PET measures cerebral glucose metabolism (rCMRGlc). We hypothesize that microglial activation is an early event in the Parkinson's disease (PD) spectrum and is independent of the amyloid pathology. The aim of this study is to evaluate in vivo the relationship between microglial activation, amyloid deposition, and glucose metabolism in Parkinson's disease dementia (PDD) and PD subjects without dementia. Here, we evaluated 11 PDD subjects, 8 PD subjects without dementia, and 24 control subjects. Subjects underwent T1 and T2 MRI, [C-11](R)PK11195, [F-18]FDG, and [C-11]PIB PET scans. Parametric maps of [C-11](R)PK11195 binding potential, rCMRGlc, and [C-11]PIB uptake were interrogated using region of interest and SPM (statistical parametric mapping) analysis. The PDD patients showed a significant increase of microglial activation in anterior and posterior cingulate, striatum, frontal, temporal, parietal, and occipital cortical regions compared with the controls. The PD subjects also showed a statistically significant increase in microglial activation in temporal, parietal, and occipital regions. [C-11]PIB uptake was marginally increased in PDD and PD. There was a significant reduction in glucose metabolism in PDD and PD. We have also demonstrated pixel-by-pixel correlation between mini-mental state examination (MMSE) score and microglial activation, and MMSE score and rCMRGlc. In conclusion, we have demonstrated that cortical microglial activation and reduced glucose metabolism can be detected early on in this disease spectrum. Significant microglial activation may be a factor in driving the disease process in PDD. Given this, agents that affect microglial activation could have an influence on disease progression. Neuropsychopharmacology (2013) 38, 938-949; doi:10.1038/npp.2012.255; published online 16 January 2013