Higher levels of different muscarinic receptors in the cortex and hippocampus from subjects with Alzheimer’s disease

It has been suggest that drugs specifically targeting muscarinic receptors will be useful in treating Alzheimer’s disease. We decided to determine if the response to such drugs may be altered, because of changes in the levels of muscarinic receptors in the CNS from subjects with the disorder. We used in situ radioligand binding with autoradiography to measure the levels of [³H]pirenzepine binding to muscarinic M1 receptors, [³H]AF-DX 386 binding to muscarinic M1, M2, and M4 receptors, and [³H]4-DAMP binding to muscarinic M1 and M3 receptors in the dorsolateral prefrontal cortex and hippocampus from subjects with Alzheimer’s and age/sex-matched controls. Compared with controls, [³H]pirenzepine binding was higher in the dentate gyrus from subjects with Alzheimer’s disease. [³H]AF-DX 386 binding was higher in the subiculum and parahippocampal gyrus from subjects with the disorder. In Alzheimer’s disease, [³H]-DAMP binding was higher in the dorsolateral prefrontal cortex but not different in the hippocampus. Our data show complex changes in the levels of muscarinic receptors in the CNS from subjects with Alzheimer’s disease which may affect clinical response to treatment with drugs-targeting these receptors.