Discovery of boronic acid-based fluorescent probes targeting amyloid-beta plaques in Alzheimer's disease

A boronic acid-based fluorescent probe was developed for diagnosis of amyloid-beta (A beta) plaques from Alzheimer's disease (AD). Probe 4c, which included boronic acid as a functional group, exhibited a significant increase (64.37-fold, F-A beta/F-0) in fluorescence intensity as a response to A beta aggregates, with a blue shift (105 nm) in the maximum emission wavelength. We found that boronic acid as a functional group improved the binding affinity (K-D value = 0.79 +/- 0.05 mu M for 4c) for A beta aggregates and confirmed that 4c selectively stained A beta plaques in brain sections from APP/PS1 mice. Ex vivo fluorescence imaging using mice (normal and APP/PS1) also revealed that 4c was able to penetrate the blood-brain barrier (BBB) and to stain A beta plaques in the brain. From these results, we believe that 4c will be useful as a fluorescent probe in preclinical research related to AD. Furthermore, we believe that our results with boronic acid also provide valuable information for the development of a probe for A beta plaques. (C) 2016 Published by Elsevier Ltd.