Nicotinic Receptors, Amyloid-beta, and Synaptic Failure in Alzheimer's Disease

Dysfunctional cholinergic transmission is thought to underlie, at least in part, memory impairment and cognitive deficits in Alzheimer's disease (AD). However, it is still unclear whether this is a consequence of the loss of cholinergic neurons and elimination of nicotinic acetycholine receptors (nAChRs) in AD brain or of a direct impact of molecular interactions of the amyloid-beta (A beta) peptide with nAChRs, leading to dysregulation of receptor function. This review examines recent progress in our understanding of the roles of nicotinic receptors in mechanisms of synaptic plasticity, molecular interactions of A beta with nAChRs, and how A beta-induced dysregulation of nicotinic receptor function may underlie synaptic failure in AD.