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

Abstract

Cholinesterases are involved in the pathological formation of beta-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 beta-amyloid plaques. Unexpectedly, it was discovered, by competition experiments, that the compound binds to amyloid structures, rather than to cholinesterases inside of the plaques.