Psychosis of Alzheimer's disease is associated with elevated muscarinic M2 binding in the cortex.
OBJECTIVE
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 M(1) and M(2) 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 M(1) and M(2) 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, M(2) receptor density was reduced only in the frontal cortex of AD, whereas M(1) was unaffected. Within the AD group, the neurochemical variables were not affected by demographic factors, disease severity, or cognition. Instead, M(2) 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 M(2) receptors in the psychosis of AD and may provide the rationale for treatment of behaviorally perturbed patients with AD with cholinomimetics and M(2) antagonists.
Lai
M K
MK
Neurodegenerative Diseases Program, Department of Neurology, Singapore General Hospital, Singapore.
Lai
O F
OF
Keene
J
J
Esiri
M M
MM
Francis
P T
PT
Hope
T
T
Chen
C P
CP
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000523:psychology; D000704:Analysis of Variance; D002540:Cerebral Cortex / Q000378:metabolism*; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism; D006801:Humans; D008297:Male; D011446:Prospective Studies; D011485:Protein Binding; D011618:Psychotic Disorders / Q000378:metabolism* / Q000523:psychology; D043643:Receptor, Muscarinic M1; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic / Q000378:metabolism*; D012044:Regression Analysis; D013702:Temporal Lobe / Q000378:metabolism
D043643:Receptor, Muscarinic M1; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic