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From the Neurodegenerative Diseases Program (M.K.P. Lai and Dr. Chen), Department of Neurology, and Department of Clinical Research (O.-F. Lai), Singapore General Hospital, Singapore; Department of Pharmacology (M.K.P. Lai), University of Sydney, New South Wales, Australia; Departments of Psychiatry (Drs. Keene and Hope), Neuropathology (Dr. Esiri), and Ethox (Dr. Hope), Institute of Health Sciences, University of Oxford, UK; and the Dementia Research Laboratory (Dr. Francis), Centre for Neuroscience Research, GKT School of Biomedical Sciences, King’s College London, UK.
Address correspondence and reprint requests to Dr. Christopher P. L.-H. Chen, MRCP, Neuroscience Research Laboratory, Department of Neurology, Block 6, Level 6, Room A5, Singapore General Hospital, Outram Road, Singapore 169608; e-mail: admin{at}neurochemalz.org
Objectives: — Results from recent drug trials suggest a role for the cholinergic system in the manifestation of neuropsychiatric symptoms in AD. To date, the status of muscarinic acetylcholine receptor subtypes in AD in relation to accompanying behavioral disturbances is unknown. This study aimed to measure alterations of muscarinic M1 and M2 receptor binding in the frontal and temporal cortex of AD and to correlate the neurochemical findings with clinical features.
Methods: — The cognitive and behavioral features of 26 patients with AD were assessed prospectively using standardized tests. Together with 14 matched controls, the status of muscarinic M1 and M2 receptors in the postmortem frontal and temporal cortex of these patients were measured by radioligand binding assays and were correlated with clinical data.
Results: — Compared with controls, M2 receptor density was reduced only in the frontal cortex of AD, whereas M1 was unaffected. Within the AD group, the neurochemical variables were not affected by demographic factors, disease severity, or cognition. Instead, M2 receptor density was increased in the frontal and temporal cortex of patients with AD with psychotic symptoms compared with those without these symptoms.
Conclusions: — This study suggests a role for M2 receptors in the psychosis of AD and may provide the rationale for treatment of behaviorally perturbed patients with AD with cholinomimetics and M2 antagonists.
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