α7-nicotinic acetylcholine receptors mediate an Aβ1-42-induced increase in the level of acetylcholinesterase in primary cortical neurons

The â-amyloid protein (Aâ) is the major protein component of amyloid plaques found in the Alzheimer brain. Although there is a loss of acetylcholinesterase (AChE) from both cholinergic and non-cholinergic neurones in the brain of Alzheimer patients, the level of AChE is increased around amyloid plaques. Previous studies using P19 cells in culture and transgenic mice which overexpress human Aâ have suggested that this increase may be due to a direct action of Aâ on AChE expression in cells adjacent to amyloid plaques. The aim of the present study was to examine the mechanism by which Aâ increases levels of AChE in primary cortical neurones. Aâ1-42 was more potent than Aâ1-40 in its ability to increase AChE in primary cortical neurones. The increase in AChE was unrelated to the toxic effects of the Aâ peptides. The effect of Aâ1-42 on AChE was blocked by inhibitors of á7 nicotinic acetylcholine receptors (á7 nAChRs) as well as by inhibitors of L- or N-type voltage-dependent calcium channels (VDCCs), whereas agonists of á7 nAChRs (choline, nicotine) increased the level of AChE. The results demonstrate that the effect of Aâ1-42 on AChE is due to an agonist effect of Aâ1-42 on the á7 nAChR.