Development of fluorescent probes that bind and stain amyloid plaques in Alzheimer's disease.

β-amyloid (Aβ) plaques in the brain are composed of Aβ40 and Aβ42 peptides, and are the defining pathological feature of Alzheimer's disease (AD). Fluorescent probes that can detect Aβ plaques have gained increasing interest as potential tools for in vitro and in vivo monitoring of the progression of AD. In this study, chalcone-mimic fluorescent probe 5 was designed and prepared. Probe 5 exhibited an approximately 50-fold increase in emission intensity after mixing with Aβ42 aggregates, a high affinity for Aβ42 aggregates (K D = 1.59 μM), and reasonable lipophilicity (log P value = 2.55). Probe 5 also exhibited specific staining of Aβ plaques in the transgenic mice (APP/PS1) brain sections. Ex vivo fluorescence imaging of the brain from normal and TG mice revealed that probe 5 was able to penetrate the BBB and stain the Aβ plaques. These results suggest that chalcone-mimic probe 5 possessed the requirements of a fluorescent probe for Aβ plaques and may be useful in AD research.