Molecular mechanism of amyloid β-peptide-induced impairment of neurotransmission and memory in relation to oxidative stress

IMPAIRMENT OF CHOLINERGIC NEUROTRANSMISSION INDUCED BY Aβ Since the cholinergic hypothesis of AD was proposed, the question of whether Aβ impairs cholinergic neurotransmission is compelling. To assess the cholinergic neurotransmission in Aβinfused rats, we used a microdialysis technique to examine acetylcholine (ACh) release under nicotine stimulation.9,10 The amplitude of the nicotine-evoked ACh release was no different between naive rats and rats receiving either vehicle or the non-toxic reverse fragment Aβ401, whereas neurotoxic Aβ fragments, including Aβ1-42, Aβ1-40 and Aβ25-35, resulted in a marked decrease in nicotine-stimulated ACh release compared with Aβ40-1-infused control rats.9,10 These findings suggest that only neurotoxic fragments of Aβ impaired nicotine-evoked ACh release and cognitive function.