Neuronal nicotinic acetylcholine receptors serve as sensitive targets that mediate β-amyloid neurotoxicity

Alzheimer's disease (AD) is the most common form of brain dementia characterized by the accumulation of beta-amyloid peptides (A beta) and loss of forebrain cholinergic neurons. A beta accumulation and aggregation are thought to contribute to cholinergic neuronal degeneration, in turn causing learning and memory deficits, but the specific targets that mediate A beta neurotoxicity remain elusive. Recently, accumulating lines of evidence have demonstrated that A beta directly modulates the function of neuronal nicotinic acetylcholine receptors (nAChRs), which leads to the new hypothesis that neuronal nAChRs may serve as important targets that mediate A beta neurotoxicity. In this review, we summarize current studies performed in our laboratory and in others to address the question of how A beta modulates neuronal nAChRs, especially nAChR subunit function.