Novel fluorescence probes based on the chalcone scaffold for in vitro staining of β-amyloid plaques

The β-amyloid (Aβ) plaque is one of the neuropathological hallmarks in the Alzheimer's disease brain. The detection of Aβ plaques with fluorescence probes is useful for preclinical studies of Alzheimer's disease. In this study, we developed four novel fluorescence probes based on chalcone scaffold. In an in vitro binding study, all FCH derivatives showed moderate binding affinity for Aβ(1-42) aggregates (K_i = 72-114 nM). The fluorescence intensities of FCH-3 and FCH-4 dramatically changed in the presence of Aβ(1-42) aggregates (6.7 and 14.2 fold), but the changes of FCH-1 and FCH-2 were minor (2.0 and 2.4 fold). In a fluorescence staining study using Tg2576 mouse brain sections, FCH-3 and FCH-4 clearly visualized Aβ plaques, but FCH-1 and FCH-2 did not stain. Taken together, all FCH derivatives could bind to Aβ aggregates, but only FCH-3 and FCH-4 may be useful fluorescence probes for in vitro staining of Aβ plaques.