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

beta-amyloid (A beta) plaques in the brain are composed of A beta(40) and A beta(42) peptides, and are the defining pathological feature of Alzheimer's disease (AD). Fluorescent probes that can detect A beta 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 A beta(42) aggregates, a high affinity for A beta(42) aggregates (K (D) = 1.59 mu M), and reasonable lipophilicity (log P value = 2.55). Probe 5 also exhibited specific staining of A beta 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 A beta plaques. These results suggest that chalcone-mimic probe 5 possessed the requirements of a fluorescent probe for A beta plaques and may be useful in AD research.