β-Amyloid aggregation induced by human acetylcholinesterase: inhibition studies

Abstract

The aggregation of β-amyloid (1–40) (Aβ) induced by human recombinant acetylcholinesterase (HuAChE) was studied by means of circular dichroism (CD) and by thioflavin T fluorescence spectroscopy. Aβ was incubated alone and with HuAChE. The kinetic of fibrils formation was followed for 48 hr. The increasing β-conformation content induced by HuAChE, preliminary to the formation of Aβ fibrils, was determined by circular dichroism. This phenomenon was found to be related to the thioflavin T emission of fluorescence at 490 nm. Incubation experiments were performed in the presence of known AChE inhibitors (physostigmine, edrophonium, decamethonium, propidium) and drugs used for Alzheimer’s disease (AD) (tacrine, donepezil), to test their capability of preventing the HuAChE-induced Aβ aggregation. The non-competitive or mixed mode of AChE inhibition was confirmed to be an essential feature. At 100 μM propidium, decamethonium, donepezil and physostigmine were found to inhibit the HuAChE-induced Aβ aggregation by 82, 25, 22 and 30%, respectively.