Two features of Alzheimer's disease (AD) are beta-amyloid protein (betaAP) 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 betaAP is suggested by a negative correlation between cigarette smoking and AD. Evidence hitherto suggests that betaAP 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 can partially prevent the neurotoxicity of betaAP 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 betaAP neurotoxicity and nicotinic intervention as a protective agent are discussed.