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)=1.84 μM) 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.
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