A novel BODIPY-based theranostic agent for in vivo fluorescence imaging of cerebral A and ameliorating A-associated disorders in Alzheimer's disease transgenic mice

beta-Amyloid (A beta) aggregation is increasingly recognized as both a biomarker and an inducer of the progression of Alzheimer's disease (AD). Here, we describe a novel fluorescent probe P14, developed based on the BODIPY structure, capable of simultaneous visualization and inhibition of A beta aggregation in vivo. P14 shows high binding affinity to A beta aggregates and selectively labels A beta plaques in the brain slices of APP/PS1 mice. Moreover, P14 is able to visualize overloaded A beta in both APP/PS1 and 5 x FAD transgenic mice in vivo. From the aspect of potential therapeutic effects, P14 administration inhibits A beta aggregation and alleviates A beta-induced neuronal damage in vitro, as well as reduces central A beta deposition and ameliorates cognitive impairment in APP/PS1 transgenic mice in vivo. Finally, P14 is applied to monitor the progression of A beta aggregation in the brain of 5 x FAD transgenic mice and the intervention effect itself by fluorescence imaging. In summary, the discovery of this fluorescent agent might provide important clues for the future development of theranostic drug candidates targeting A beta aggregation in AD.