Autoradiographic distribution of M1, M2, M3, and m4 muscarinic receptor subtypes in Alzheimer's disease

Abstract

We studied the autoradiographic densities of all pharmacologically characterized muscarinic receptors (MR) in frontal, temporal, and visual cortex, hippocampal formation, and striatum in autopsied brains from 19 histopathologically verified patients of Alzheimer's disease (AD) and in matched controls. Almost all (16 of 19) of the AD cases were severe. In AD brains, total MR, M1, and M3 MR subtypes were found to be significantly decreased in entorhinal cortex and in most hippocampal strata. Total MR and M1 receptors were also significantly reduced in visual area and in frontal cortex of AD brains, respectively. M2 receptors were significantly reduced over hippocampal formation but increased significantly in striatum of AD brains as compared with controls. M3 receptors in AD were in the range of controls in neocortex and striatum, whereas the M4 receptor subtype was also preserved in all brain regions in AD brains when compared with controls. This is the first autoradiographic study analysing the distribution of all MR subtypes in AD brains. These changes in MR densities concur with the general pattern of neuronal degeneration occurring in AD brains and partly explain the poor response of AD cognitive decline to present cholinergic supplementation therapies. Although M3 and M4 MR were labelled with nonselective approaches, the preservation of M4 and to a lesser degree M3 MR subtypes in AD brains could open an alternative way for the symptomatic therapy of AD dementia.