Venneti Sriram, Lopresti Brian J, Wang Guoji, Hamilton Ronald L, Mathis Chester A, Klunk William E, Apte Udayan M, Wiley Clayton A
Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
Neurobiol Aging. 2009 Aug;30(8):1217-26. doi: 10.1016/j.neurobiolaging.2007.11.005. Epub 2008 Feb 21.
Activated microglia may promote neurodegeneration in Alzheimer's disease (AD) and may also help in amyloid clearance in immunization therapies. In vivo imaging of activated microglia using positron emission tomography (PET) could assist in defining the role of activated microglia during AD progression and therapeutics. We hypothesized that PK11195, a ligand that binds activated microglia, could label these cells in postmortem AD tissues and in vivo in an animal model of AD using PET. (3)H-PK11195 binding was significantly higher in AD frontal cortex compared to controls and correlated mainly with the abundance of immunohistochemically labeled activated microglia. With age, the brains of APP/PS1 transgenic mice showed progressive increase in (3)H-PK11195 binding and (11)C-PK11195 retention in vivo assessed using microPET, which correlated with the histopathological abundance of activated microglia. These results suggest that PK11195 binding in AD postmortem tissue and transgenic mice in vivo correlates with the extent of microglial activation and may help define the role of activated microglia in the pathogenesis and treatment of AD.
活化的小胶质细胞可能在阿尔茨海默病（AD）中促进神经退行性变，也可能在免疫治疗中有助于淀粉样蛋白清除。使用正电子发射断层扫描（PET）对活化的小胶质细胞进行体内成像，有助于明确活化的小胶质细胞在AD进展和治疗过程中的作用。我们假设，PK11195，一种与活化的小胶质细胞结合的配体，能够在AD死后组织以及使用PET的AD动物模型体内标记这些细胞。与对照组相比，AD额叶皮质中³H-PK11195结合显著更高，且主要与免疫组织化学标记的活化小胶质细胞丰度相关。随着年龄增长，APP/PS1转基因小鼠的大脑中，使用微型PET评估显示，体内³H-PK11195结合和¹¹C-PK11195滞留逐渐增加，这与活化小胶质细胞的组织病理学丰度相关。这些结果表明，AD死后组织和转基因小鼠体内的PK11195结合与小胶质细胞活化程度相关，可能有助于明确活化的小胶质细胞在AD发病机制和治疗中的作用。
