A conformationally-locked p-hydroxybenzylidene imidazolinone derivative for detecting Aβ₄₂ aggregation

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 Aβ species, amyloid-β ₄₂ (Aβ₄₂) aggregates are proposed to be more neurotoxic than that of Aβ₄₀, and oligomeric Aβ₄₂ is thought to play a harmful role in the pathophysiology of AD. Therefore, the detection of Aβ₄₂ 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 Aβ₄₂ 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 Aβ₄₂ aggregation over that of Aβ₄₀ in the brain tissues of AD transgenic mouse models. Therefore, this new probe could provide a useful tool for the rapid detection of important Aβ species in AD.