Can Activation of Acetylcholinesterase by β-Amyloid Peptide Decrease the Effectiveness of Cholinesterase Inhibitors?

A central event in the pathogenesis of Alzheimer's disease (AD) is the accumulation of senile plaques composed of aggregated amyloid-β (Aβ) peptides. The main class of drugs currently used for the treatment of AD are the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors. In this study, it has been shown that Aβ augmented AChE activity in vitro, maximum activation of 548 ± 5% was achieved following 48 h of incubation with 10 μM of Aβ 1-40 , leading to a 7.7-fold increase in catalytic efficiency. The observed non-competitive type of AChE activation by Aβ 1-40 was associated with increased V max and unchanged K m . Although BChE activity also increased following incubation with Aβ 1-40 , this was less efficiently achieved as compared with AChE. Ex vivo electrophysiological experiments showed that 10 μM of Aβ 1-40 significantly decreased the effect of the AChE inhibitor huperzine A on the synaptic potential parameters.