The nicotinic acetylcholine receptor, smoking, and Alzheimer's disease.
Cholinergic dysfunction is one of the cornerstones of Alzheimer's disease (AD) pathology. Reviewed here is evidence evaluating relationships between smoking, nicotine exposure, nicotinic cholinergic signaling, and AD. Epidemiological studies initially indicating a lower incidence of AD in smokers now suggest conflicting results. Clinicopathological findings also are mixed as to how smoking behavior affects manifestation of AD markers. Studies that show nicotine-induced increases in nicotinic acetylcholine receptors (nAChR) and protection against age-related nAChR decline contrast, perhaps in a functionally relevant way, to losses of nAChR in AD. Although epidemiological, clinicopathological, and functional studies in humans do not present a cohesive picture, much in vitro data suggests neuroprotective properties of nicotine when used in models of neurodegenerative disorders. Studies of nicotine and nicotinic agonist effects on cognitive function in the non-demented and in AD are not compelling. More work is needed to ascertain whether acute or repetitive activation of nAChR with acute or intermittent exposure to nicotine or the persistent inactivation of nAChR with chronic nicotine exposure is a therapeutic objective and/or explains any pro-cognitive effects of those drugs. Other studies show complex interactions between nAChR, nicotinic agonists, and agents implicated in AD etiology. Thus, while controversies still exist, ongoing research is illuminating how nicotinic receptor changes and functions may be relevant to clinical, pathological and neurochemical changes that occur in AD.
Sabbagh
Marwan N
MN
The Cleo Roberts Center for Clinical Research, Sun Health Research Institute, Sun City, AZ 85351, USA. marwan.sabbagh@sunhealth.org
Lukas
Ronald J
RJ
Sparks
D Larry
DL
Reid
Richard T
RT
D000544:Alzheimer Disease / Q000503:physiopathology*; D000818:Animals; D001921:Brain / Q000503:physiopathology; D006801:Humans; D009474:Neurons / Q000502:physiology; D011978:Receptors, Nicotinic / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D012907:Smoking / Q000503:physiopathology*
D011978:Receptors, Nicotinic