The nicotinic acetylcholine receptor: smoking and Alzheimer's disease revisited

Epidemiological studies regarding Alzheimer's disease (AD) in smokers currently suggest inconsistent results. The clinicopathological findings also vary as to how AD pathology is affected by smoking behavior. Even though clinicopathological, functional, and epidemiological studies in humans do not present a consistent picture, much of the in vitro data implies that nicotine has neuroprotective effects when used in neurodegenerative disorder models. Current studies of the effects of nicotine and nicotinic agonists on cognitive function in both the non-demented and those with AD are not convincing. More data is needed to determine whether repetitive activation of nAChR with intermittent or acute exposure to nicotine, acute activation of nAChR, or long-lasting inactivation of nAChR secondary to chronic nicotine exposure will have a therapeutic effect and/or explain the beneficial effects of those types of drugs. Other studies show multifaceted connections between nicotine, nicotinic agonists, smoking, and nAChRs implicated in AD etiology. Although many controversies still exist, ongoing studies are revealing how nicotinic receptor changes and functions may be significant to the neurochemical, pathological, and clinical changes that appear in AD.