AUTORADIOGRAPHIC DISTRIBUTION OF M1, M2, M3, AND M4 MUSCARINIC RECEPTOR SUBTYPES IN ALZHEIMERS-DISEASE

We studied the autoradiographic densities of all pharmacologically cha racterised muscarinic receptors (MR) in frontal, temporal, and visual cortex, hippocampal formation, and striatum in autopsied brains from 1 9 histopathologically verified patients of Alzheimer's disease (AD) an d in matched controls. Almost all (16 of 19) of the AD cases were seve re. In AD brains, total MR, M1, and M3 MR subtypes were found to be si gnificantly decreased in entorhinal cortex and in most hippocampal str ata. Total MR and M1 receptors were also significantly reduced in visu al area and in frontal cortex of AD brains, respectively. M2 receptors were significantly reduced over hippocampal formation but increased s ignificantly in striatum of AD brains as compared with controls. M3 re ceptors in AD were in the range of controls in neocortex and striatum, whereas the M4 receptor subtype was also preserved in all brain regio ns in AD brains when compared with controls. This is the first autorad iographic study analysing the distribution of all MR subtypes in AD br ains. These changes in MR densities concur with the general pattern of neuronal degeneration occurring in AD brains and partly explain the p oor response of AD cognitive decline to present cholinergic supplement ation therapies. Although M3 and M4 MR were labelled with nonselective approaches, the preservation of M4 and to a lesser degree M3 MR subty pes in AD brains could open an alternative way for the symptomatic the rapy of AD dementia. (C) 1997 Wiley-Liss, Inc.