Search

A boronic acid-based fluorescent probe was developed for diagnosis of amyloid-β (Aβ) plaques from Alzheimer’s disease (AD). Probe 4c , which included boronic acid as a functional group, exhibited a significant increase (64.37-fold, F Aβ / F 0 ) in fluorescence intensity as a response to Aβ 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 μM for 4c ) for Aβ aggregates and confirmed that 4c selectively stained Aβ 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 Aβ 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 Aβ plaques. [ABSTRACT FROM AUTHOR]

Abstract: Amyloid plaques, which are primarily composed of aggregated amyloid-beta (Aβ) peptide, are the neuropathological hallmarks of Alzheimer’s disease (AD). Fluorescent markers containing 2-styrylpyridazin-3(2H)-ones were developed to detect intracellular aggregated Aβ peptides. Nine compounds exhibited a greater than 10-fold increase of in emission spectra before and after mixing with Aβ aggregates compared with before mixing. Among these compounds, compound 9n exhibited the highest affinity for Aβ aggregates (K d =1.84μM) and selectively stained both aggregated intracellular Aβ and Aβ plaques in the transgenic AD model mice (APP/PS1). These preliminary results indicate that 2-styrylpyridazin-3(2H)-one derivatives are promising alternative fluorescence imaging agent for the study of AD. [Copyright &y& Elsevier]