Nicotine modulates the neurotoxic effect of β-amyloid protein(25–35) in hippocampal cultures

TWO major features of Alzheimerʼs disease (AD) are b-amyloid protein (βAP) deposition and a severe cholinergic deficit. An association between the two is suggested by the negative correlation found between cigarette smoking and AD. We sought to investigate this further by examining the effects of acute and chronic nicotine exposure on βAP-induced neuronal loss in rat hippocampal cultures. Nicotine was found to attenuate the neurotoxicity of higher concentrations of βAP(25–35), an effect which was enhanced by longer nicotine pretreatment and significantly inhibited by the nicotine receptor antagonist mecamylamine. Our results suggest that nicotine partially protects against the neurotoxic actions of βAP(25–35) via a receptor-mediated pathway.