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In-vitro and in-vivo characterization of CRANAD-2 for multi-spectral optoacoustic tomography and fluorescence imaging of amyloid-beta deposits in Alzheimer mice
Photoacoustics ( IF 7.1 ) Pub Date : 2021-07-15 , DOI: 10.1016/j.pacs.2021.100285
Ruiqing Ni 1, 2, 3 , Alessia Villois 4 , Xose Luis Dean-Ben 1, 5 , Zhenyue Chen 1, 5 , Markus Vaas 1 , Stavros Stavrakis 4 , Gloria Shi 1 , Andrew deMello 4 , Chongzhao Ran 6 , Daniel Razansky 1, 3, 5 , Paolo Arosio 4 , Jan Klohs 1, 3
Affiliation  

The abnormal deposition of fibrillar beta-amyloid (Aβ) deposits in the brain is one of the major histopathological hallmarks of Alzheimer’s disease (AD). Here, we characterized curcumin-derivative CRANAD-2 for multi-spectral optoacoustic tomography and fluorescence imaging of brain Aβ deposits in the arcAβ mouse model of AD cerebral amyloidosis. CRANAD-2 showed a specific and quantitative detection of Aβ fibrils in vitro, even in complex mixtures, and it is capable of distinguishing between monomeric and fibrillar forms of Aβ. In vivo epi-fluorescence microscopy and optoacoustic tomography after intravenous CRANAD-2 administration demonstrated higher cortical retention in arcAβ compared to non-transgenic littermate mice. Immunohistochemistry showed co-localization of CRANAD-2 and Aβ deposits in arcAβ mouse brain sections, thus verifying the specificity of the probe. In conclusion, we demonstrate suitability of CRANAD-2 for optical detection of Aβ deposits in animal models of AD pathology, which facilitates mechanistic studies and the monitoring of putative treatments targeting Aβ deposits.



中文翻译:

CRANAD-2 的体外和体内表征用于阿尔茨海默病小鼠淀粉样蛋白沉积物的多光谱光声断层扫描和荧光成像

大脑中纤维状 β-淀粉样蛋白 (Aβ) 沉积物的异常沉积是阿尔茨海默病 (AD) 的主要组织病理学标志之一。在这里,我们表征了姜黄素衍生物 CRANAD-2,用于 AD 脑淀粉样变性 arcAβ 小鼠模型中脑 Aβ 沉积物的多光谱光声断层扫描和荧光成像。CRANAD-2 显示了体外Aβ 原纤维的特异性和定量检测即使在复杂的混合物中,它也能够区分 Aβ 的单体和原纤维形式。体内与非转基因同窝小鼠相比,静脉注射 CRANAD-2 后的落射荧光显微镜和光声断层扫描表明 arcAβ 中的皮质保留更高。免疫组织化学显示,在 arcAβ 小鼠脑切片中,CRANAD-2 和 Aβ 沉积物共定位,从而验证了探针的特异性。总之,我们证明了 CRANAD-2 适用于 AD 病理动物模型中 Aβ 沉积物的光学检测,这有助于机制研究和监测针对 Aβ 沉积物的假定治疗。

更新日期:2021-07-20
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