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

β-Amyloid (Aβ) 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 Aβ aggregation in vivo. P14 shows high binding affinity to Aβ aggregates and selectively labels Aβ plaques in the brain slices of APP/PS1 mice. Moreover, P14 is able to visualize overloaded Aβ in both APP/PS1 and 5 × FAD transgenic mice in vivo. From the aspect of potential therapeutic effects, P14 administration inhibits Aβ aggregation and alleviates Aβ-induced neuronal damage in vitro, as well as reduces central Aβ deposition and ameliorates cognitive impairment in APP/PS1 transgenic mice in vivo. Finally, P14 is applied to monitor the progression of Aβ aggregation in the brain of 5 × 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 Aβ aggregation in AD.