Nicotine and its interaction with β-amyloid protein:: A short review

Two features of Alzheimer's disease (AD) are beta -amyloid protein (beta AP) deposition and a severe cholinergic deficit. beta -Amyloid protein is a 39- to 43-amino acid transmembrane fragment of a larger precursor molecule, amyloid precursor protein. It is a major constituent of senile plaque, a neuropathologic hallmark of AD, and has been shown to be neurotoxic in vivo and in vitro. The cholinergic neurotransmission system is seen as the primary target of AD. However other systems are also found to show functional deficit. An association between cholinergic deficit and beta AP is suggested by a negative correlation bern,een cigarette smoking and AD. Evidence hitherto suggests that beta AP causes neuronal death possibly via apoptosis by disrupting calcium homeostasis, which may involve direct activation or enhancement of ligand-gated or voltage-dependent calcium channels. Selective second messengers such as protein kinases are triggered that signal neuronal death. Nicotine or acetylcholinesterase inhibitors call partially prevent the neurotoxicity of beta AP in vivo and in vitro. However, the exact mechanism by, which nicotine provides its protective effects is not fully understood, but clearly there are protective roles for nicotine. Here, some aspects of beta AP neurotoxicity and nicotinic intervention as a protective agent are discussed. (C) 2001 Society of Biological Psychiatry.