Psychosis of Alzheimer's disease is associated with elevated muscarinic M-2 binding in the cortex

Objectives: Results from recent drug trials suggest a role for the choliner gic system in the manifestation of neuropsychiatric symptoms in AD. To date , the status of muscarinic acetylcholine receptor subtypes in AD in relatio n to accompanying behavioral disturbances is unknown. This study aimed to m easure alterations of muscarinic M-1 and M-2 receptor binding in the fronta l and temporal cortex of AD and to correlate the neurochemical findings wit h clinical features. Methods: The cognitive and behavioral features of 26 p atients with AD were assessed prospectively using standardized tests. Toget her with 14 matched controls, the status of muscarinic M-1 and M-2 receptor s in the postmortem frontal and temporal cortex of these patients were meas ured by radioligand binding assays and were correlated with clinical data. Results: Compared with controls, M-2 receptor density was reduced only in t he frontal cortex of AD, whereas M-1 was unaffected, Within the AD group, t he neurochemical variables were not affected by demographic factors, diseas e severity, or cognition. Instead, M-2 receptor density was increased in th e frontal and temporal cortex of patients with AD with psychotic symptoms c ompared with those without these symptoms. Conclusions: This study suggests a role for M-2 receptors in the psychosis of AD and may provide the ration ale for treatment of behaviorally perturbed patients with AD with cholinomi metics and M-2 antagonists.