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.

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。