Loss of muscarinic M4 receptors in hippocampus of Alzheimer patients

We assessed muscarinic M1, M2 and M4 receptor subtypes in the hippocampus of Alzheimer's and control brains by receptor autoradiography using ligands such as [125I]muscarinic toxin-1 ([125I]MT-1, M1 selective), [3H]AFDX-384 (M2 partially selective) and [125I]muscarinic toxin 4 ([125I]M4 toxin-1, M4 selective). Our results revealed a significant decrease in muscarinic M4 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 M1 or M2 receptor binding were observed. Our findings suggest that, relative to other muscarinic receptor subtypes, the M4 receptor could be the subtype which is selectively compromised in Alzeheimer's disease (AD). © 2002 Published by Elsevier Science B.V.