A gorge-spanning, high-affinity cholinesterase inhibitor to explore β-amyloid plaques

Abstract

Cholinesterases are involved in the pathological formation of β-amyloid plaques. To investigate this pathohistological hallmark of Alzheimer's disease we prepared a high-affinity, fluorescent cholinesterase inhibitor. Its fluorescence intensity was significantly enhanced upon binding to cholinesterases. Using this probe, brain samples from mice and humans affected by Alzheimer's disease were successfully analyzed for β-amyloid plaques. Unexpectedly, it was discovered, by competition experiments, that the compound binds to amyloid structures, rather than to cholinesterases inside of the plaques.