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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Four-dimensional multiphoton imaging of brain entry, amyloid binding, and clearance of an amyloid-β ligand in transgenic mice
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Four-dimensional multiphoton imaging of brain entry, amyloid binding, and clearance of an amyloid-β ligand in transgenic mice

机译：转基因小鼠大脑进入，淀粉样蛋白结合和淀粉样β配体清除的四维多光子成像

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摘要

The lack of a specific biomarker makes preclinical diagnosis of Alzheimer's disease (AD) impossible, and it precludes assessment of therapies aimed at preventing or reversing the course of the disease. The development of a tool that enables direct, quantitative detection of the amyloid-β deposits found in the disease would provide an excellent biomarker. This article demonstrates the real-time biodistribution kinetics of an imaging agent in transgenic mouse models of AD. Using multiphoton microscopy, Pittsburgh compound B (PIB) was imaged with sub-μm resolution in the brains of living transgenic mice during peripheral administration. PIB entered the brain quickly and labeled amyloid deposits within minutes. The nonspecific binding was cleared rapidly, whereas specific labeling was prolonged. WT mice showed rapid brain entry and clearance of PIB without any binding. These results demonstrate that the compound PIB has the properties required for a good amyloid-imaging agent in humans with or at risk for AD.
机译：缺乏特定的生物标记物使得不可能进行阿尔茨海默氏病（AD）的临床前诊断，并且排除了评估旨在预防或逆转疾病进程的疗法的可能性。开发一种能够直接，定量检测该疾病中发现的淀粉样β沉积物的工具将提供出色的生物标记。本文演示了成像剂在AD转基因小鼠模型中的实时生物分布动力学。使用多光子显微镜，匹兹堡化合物B（PIB）在外周给药期间在活的转基因小鼠的大脑中以亚微米分辨率成像。 PIB迅速进入大脑，并在几分钟内标记出淀粉样蛋白沉积物。非特异性结合被迅速清除，而特异性标记被延长。野生型小鼠表现出快速的大脑进入和PIB清除没有任何绑定。这些结果表明，化合物PIB具有在患有AD或有AD风险的人中良好的淀粉样蛋白成像剂所需的性质。

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