m2 muscarinic acetylcholine receptor-immunoreactive neurons are not reduced within the nucleus basalis in Alzheimer's disease: Relationship with cholinergic and galaninergic perikarya

Abstract

The distribution of profiles containing the m2-muscarinic acetylcholine receptor within the aged human basal forebrain and its relationship to cholinergic and noncholinerigc neurons and alterations in Alzheimer's disease (AD) was investigated by using an m2-specific monoclonal antibody (Levey et al. [1995] J. Comp. Neurol. 351:339-356). Immunocytochemistry revealed that the m2 receptor protein is expressed primarily in noncholinergic multipolar neurons (mean+/-S.E.M.; 355.7+/-15.4 microm2) located primarily outside the cholinergic nucleus basalis subfields. Dual-stained sections from the septal/diagonal band complex revealed that m2 was detected in only 14% of choline acetyltransferase-labeled neurons, whereas only 13% of m2-stained neurons colocalized choline acetyltransferase. Within the nucleus basalis, choline acetyltransferase was found in 35% of the m2-labeled neurons, whereas only 6% of choline acetyltransferase-stained perikarya were dual labeled for m2. Although we did not visualize colocalization of m2+/choline acetyltransferase-immunonegative neurons and the inhibitory neuropeptide galanin, galaninergic fibers coursed in close apposition to m2+ cells. Cell counts demonstrated that 90% of choline acetyltransferase-labeled striatal neurons expressed the m2 receptor. Despite the extensive reduction in cholinergic basal forebrain neurons, cell counts of the relative number ofm2-immunoreactive neurons within the nucleus basalis complex from aged controls and AD patients revealed that the m2 neurons are spared. Finally, our findings suggest that most m2 receptors in the cholinergic basal forebrain are located on noncholinergic structures; therefore, they are not the major source of m2 receptors in the cortex. Thus, the reduced levels of the m2 receptor seen in AD cortex probably reflect changes in other neuronal populations.