Neurotransmitter receptors in Alzheimer disease

Alzheimer disease (AD) is an exceedingly complex disorder in which numerous populations of neurons and neurotransmitter systems are damaged or destroyed. Effective treatment of the cognitive symptoms of AD does not exist, and new targets for therapeutic intervention are needed desperately. Traditionally, the neurotransmitter receptors have been the focus of new neuropsychopharmacological agents, so it seems reasonable to assess the status of these receptors in the AD brain. In this article, we review the quarter century of receptor research in AD. The limitations of receptor studies, in general, and the particular limitations of studying AD tissue are discussed. The cholinergic and glutamatergic systems have been implicated most directly in normal cognitive function, so the receptors for these neurotransmitters are emphasized in this review. We have attempted to point out the possible neurobiological roles and potential clinical significance of the various receptors in AD. Investigation of neurotransmitter receptors in AD provides a rational approach to the development of therapeutic and diagnostic strategies, and, at a minimum, should lead to a better understanding of the neurobiology of AD.