Cholinergic receptors in aging and Alzheimer's disease

Although Alzheimer's disease (AD) is a disorder involving multiple neurotransmitter systems, the basal forebrain cholinergic system (Ch system) is severely and consistently affected in this condition. In both animals and man, the nature of age-associated alterations in the Ch system is unclear. In addition, available studies of cholinergic receptors in AD and aging are not consistent. In normal aging, the density of muscarinic cholinergic receptors (MCR) is reported to be either unchanged or decreased. In AD, increased, unchanged, or decreased densities have been reported. Recently, a subtype of MCR (M2), thought to be located presynaptically, has been reported to be reduced in neocortex and amygdala. In both AD and aging, nicotinic cholinergic receptors (NCR) have not been adequately studied. Our recent studies using [3H] acetylcholine and [3H] nicotine have demonstrated a reduction in NCR in AD. Possible explanations for some of the inconsistent findings are discussed, and directions for future studies are suggested.