Design of a Coumarin-Based Fluorescent Probe for Efficient In Vivo Imaging of Amyloid-? Plaques

Amyloid-beta (A beta) is the core constituent protein of senile plaques, which is one of the key pathological hallmarks of Alzheimer's disease (AD). Here we describe the design, synthesis, and evaluation of coumarin-derived small molecule fluorophores for A beta imaging. By embedding the aromatic coumarin framework into pi bridge of a push-pull chromophore, a novel fluorescence probe XCYC-3 applicable to efficient A beta recognition was discovered. XCYC-3 displays higher fluorescent enhancement for aggregated A beta than monomeric A beta, and possesses good blood-brain barrier permeability. In vitro staining and in vivo imaging studies demonstrated that XCYC-3 could efficiently recognize A beta plaques in the brain of AD transgenic mice. These results suggest that XCYC-3 is a promising fluorescence imaging agent for A beta, which might provide important clues for the future development of potent NIR fluorescent probes for A beta diagnosis.