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

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.