Cholinergic markers in Alzheimer disease and the autoregulation of acetylcholine release.

The status of various cholinergic markers was compared in Alzheimer's and Parkinson's diseases. Rather unexpectedly, similar decrements were observed in choline acetyltransferase (ChAT) activity and in density of muscarinic M2 and nicotinic receptors in various cortical areas in these two disorders. This may relate to the existence of important functional interactions between cholinergic and dopaminergic systems in cortical and hippocampal areas. Additionally, the parallel decrements in nicotinic and muscarinic M2 receptor subtypes, with that of ChAT activities in these disorders suggest their presynaptic location. A series of pharmacological data do in fact reveal that nicotinic receptors may act as positive autoreceptors modulating basal acetylcholine release while muscarinic M2 receptors could act as negative autoreceptors. This information may have significance for the development of new treatment strategies (for example, M2 antagonists) of disorders associated with cholinergic hypofunction.