A conformationally-locked p-hydroxybenzylidene imidazolinone derivative for detecting Aß42 aggregation.

ABSTRACT

Alzheimer's disease (AD) is a common type of neurodegenerative disease, which can only be symptomatically relieved but does not yet have a cure. Among the different Aß species, amyloid-ß 42 (Aß42) aggregates are proposed to be more neurotoxic than that of Aß40, and oligomeric Aß42 is thought to play a harmful role in the pathophysiology of AD. Therefore, the detection of Aß42 aggregation is very meaningful in the AD field. We herein report a conformationally-locked p- hydroxybenzylidene imidazolinone derivative, BDI, which exhibits selectivity and specificity towards Aß42 aggregation and remarkable fluorescent enhancement with a large Stokes shift (more than 100 nm). In the fluorescent co-localization study, BDI can sensitively detect a large population of Aß42 aggregation over that of Aß40 in the brain tissues of AD transgenic mouse models. Therefore, this new probe could provide a useful tool for the rapid detection of important Aß species in AD.