Loss of muscarinic M4 receptors in hippocampus of Alzheimer patients

We assessed muscarinic M-1, M-2 and M-4 receptor subtypes in the hippocampus of Alzheimer's and control brains by receptor autoradiography using ligands such as [I-125]muscarinic toxin-1 ([I-125]MT-1, M, selective). [H-3]AFDX-384 (M-2 partially selective) and [I-125]muscarinic toxin 4 ([I-125]M-4 toxin-1, M-4 selective). Our results revealed a significant decrease in muscarinic M-4 receptor binding in the dentate gyrus and CA4 regions of brain sections from Alzheimer's patients compared to controls. No changes in the density of M-1 or M, receptor binding were observed. Our findings suggest that, relative to other muscarinic receptor subtypes, the M-4 receptor could be the subtype which is selectively compromised in Alzeheimer's disease (AD). (C) 2002 Published by Elsevier Science B.V.