Differential Alteration of Various Cholinergic Markers in Cortical and Subcortical Regions of Human Brain in Alzheimer's Disease

Abstract

The main objective of the present study was to determine whether cholinergic markers (choline acetyl-transferase activity and nicotinic and muscarinic receptors) are altered in Alzheimer's disease. Choline acetyltransferase activity in Alzheimer's brains was markedly reduced in various cortical areas, in the hippocampus, and in the nucleus basalis of Meynert. The maximal density of nicotinic sites, measured using the novel nicotinic radioligand N-[³H]methylcarbamylcholine, was decreased in cortical areas and hippocampus but not in subcortical regions. M₁ muscarinic cholinergic receptor sites were assessed using [³H]pirenzepine as a selective ligand; [³H]pirenzepine binding parameters were not altered in most cortical and subcortical structures, although the density of sites was modestly increased in the hippocampus and striatum. Finally, M₂-like muscarinic sites were studied using [³H]-acetylcholine, under muscarinic conditions. In contrast to M₁ muscarinic sites, the maximal density of M₂-like muscarinic sites was markedly reduced in all cortical areas and hippocampus but was not altered in subcortical structures. These findings reveal an apparently selective alteration in the densities of putative nicotinic and muscarinic M₂, but not M₁, receptor sites in cortical areas and in the hippocampus in Alzheimer's disease.