β -Amyloid ( A β ) plaque, representing the progressive accumulation of the protein that mainly consists of A β , is one of the prominent pathological hallmarks of Alzheimer's disease (AD). Label-free imaging of A β plaques holds the potential to be a histological examination tool for diagnosing AD. We applied label-free multiphoton microscopy to identify extracellular A β plaque as well as intracellular A β accumulation for the first time from AD mouse models. We showed that a two-photon-excited fluorescence signal is a sensitive optical marker for revealing the spatial-temporal progression and the surrounding morphological changes of A β deposition, which demonstrated that both extracellular and intracellular A β accumulations play an important role in the progression of AD. Moreover, combined with a custom-developed image-processing program, we established a rapid method to visualize different degrees of A β deposition by color coding. These results provide an approach for investigating pathophysiology of AD that can complement traditional biomedical procedures.

中文翻译：

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阿尔茨海默氏病小鼠模型中β淀粉样蛋白斑块的无标记多光子成像。

β-淀粉样蛋白（Aβ）斑块代表了主要由Aβ组成的蛋白质的逐步积累，是阿尔茨海默氏病（AD）的重要病理标志之一。Aβ斑块的无标记成像有望成为诊断AD的组织学检查工具。我们应用无标记多光子显微镜从AD小鼠模型中首次鉴定出细胞外Aβ斑块以及细胞内Aβ积累。我们表明，两光子激发的荧光信号是揭示Aβ沉积的时空进展和周围形态变化的灵敏光学标记，这表明细胞外和细胞内Aβ积累在进展中起重要作用的。此外，结合定制开发的图像处理程序，我们建立了一种快速的方法来通过颜色编码可视化不同程度的Aβ沉积。这些结果提供了一种研究AD病理生理的方法，可以补充传统的生物医学程序。