In-vitro and in-vivo characterization of CRANAD-2 for multi-spectral optoacoustic tomography and fluorescence imaging of amyloid-beta deposits in Alzheimer mice

The abnormal deposition of fibrillar beta-amyloid (A beta) 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 A beta deposits in the arcA beta mouse model of AD cerebral amyloidosis. CRANAD-2 showed a specific and quantitative detection of A beta fibrils in vitro, even in complex mixtures, and it is capable of distinguishing between monomeric and fibrillar forms of A beta. In vivo epifluorescence microscopy and optoacoustic tomography after intravenous CRANAD-2 administration demonstrated higher cortical retention in arcA beta compared to non-transgenic littermate mice. Immunohistochemistry showed co-localization of CRANAD-2 and A beta deposits in arcA beta mouse brain sections, thus verifying the specificity of the probe. In conclusion, we demonstrate suitability of CRANAD-2 for optical detection of A beta deposits in animal models of AD pathology, which facilitates mechanistic studies and the monitoring of putative treatments targeting A beta deposits.

Automated summary

The study introduces a novel optical detection method, CRANAD-2, which can specifically and quantitatively detect Aβ deposits in the brain of AD animal models, facilitating research on AD pathological mechanisms and monitoring potential treatments targeting Aβ deposits.