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

Ni, R.; Villois, A.; Dean-Ben, X. L.; Chen, Z.; Vaas, M.; Stavrakis, S.; Shi, G.; deMello, A.; Ran, C.; Razansky, D.; Arosio, P.; Klohs, J.

doi:10.1101/2020.10.27.353862

bioRxiv · 10.1101/2020.10.27.353862

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

Ni, R.·Villois, A.·Dean-Ben, X. L.·Chen, Z.·Vaas, M.·Stavrakis, S.·Shi, G.·deMello, A.·Ran, C.·Razansky, D.·Arosio, P.·Klohs, J.

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Abstract

The abnormal deposition of fibrillar beta-amyloid (A{beta}) deposits in the brain is one of the major histopathological hallmarks of Alzheimers disease (AD). Here we characterize curcumin-derivative CRANAD-2 for multi-spectral optoacoustic tomography (MSOT) and fluorescence imaging of brain A{beta} deposits in the arcA{beta} mouse model of AD cerebral amyloidosis. CRANAD-2 shows a specific and quantitative detection of A fibrils in vitro, even in complex mixtures, and it is capable to distinguish between monomeric and fibrillar forms of A. In vivo epifluorescence and MSOT after intravenous CRANAD-2 administration demonstrated higher 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 fluorescence- and MSOT-based 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.

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Ni, R., Villois, A., Dean-Ben, X. L., Chen, Z., Vaas, M., Stavrakis, S., Shi, G., deMello, A., Ran, C., Razansky, D., Arosio, P., Klohs, J.. 2020-10-28. In-vitro and in-vivo characterization of CRANAD-2 for multi-spectral optoacoustic tomography and fluorescence imaging of amyloid-beta deposits in Alzheimer mice. https://doi.org/10.1101/2020.10.27.353862

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