Nicotinic Cholinergic Mechanisms in Alzheimer's Disease

Alzheimer's disease (AD) is a neurodegenerative condition characterized by increased accumulation of Aβ and degeneration of cholinergic signaling between basal forebrain and hippocampus. Nicotinic acetylcholine receptors (nAChRs) are important mediators of cholinergic signaling in modulation of learning and memory function. Accumulating lines of evidence indicate that a nAChR subtype, α7 receptor (α7-nAChR), plays an important role in modulations of excitatory neurotransmitter release, improvement of learning and memory ability, and enhancement of cognitive function. Importantly, the expression and function of α7-nAChRs is altered in the brain of AD animal models and AD patients, suggesting that this nAChR subtype participates in AD pathogenesis and may serve as a novel therapeutic target for AD treatment. However, the mechanisms underlying the role of α7-nAChRs in AD pathogenesis are very complex, and either neuroprotective effects or neurotoxic effects may occur through the α7-nAChRs. These effects depend on the levels of α7-nAChR expression and function, disease stages, or the use of α7-nAChR agonists, antagonists, or allosteric modulators. In this chapter, we summarize recent progresses in the roles of α7-nAChRs played in AD pathogenesis and therapy.