Loss of serotonin 5-HT2A receptors in the postmortem temporal cortex correlates with rate of cognitive decline in Alzheimer's disease.
BACKGROUND
Previous studies have demonstrated reductions of serotonin 5-HT 2A receptors in the neocortex of Alzheimer's disease (AD) patients. However, it is unclear whether such losses play a role in the cognitive decline of AD.


OBJECTIVE
To correlate neocortical 5-HT 2A receptor alterations with cognitive decline in AD.


METHODS
Postmortem frontal and temporal cortical 5-HT 2A receptors were measured by [3H]ketanserin binding in aged controls as well as in a cohort of AD patients who had been longitudinally assessed for cognitive decline and behavioral symptoms.


RESULTS
5-HT 2A receptor densities in both regions were reduced in severely demented AD patients compared to age-matched controls. In the temporal cortex, this reduction also correlated with the rate of decline of Mini-Mental State Examination (MMSE) scores. The association between 5-HT 2A receptor loss and cognitive decline was independent of the effects of choline acetyltransferase (ChAT) activity and presence of behavioral symptoms.


CONCLUSIONS
Our data suggest that loss of neocortical 5-HT 2A receptors may predict for faster cognitive decline in AD, and point to serotomimetics as potentially useful adjuvants to cholinergic replacement therapies.
Lai
M K
MK
Dementia Research Laboratory, Department of Clinical Research, Singapore General Hospital, Outram Road, 169608, Singapore.
Tsang
S W
SW
Alder
J T
JT
Keene
J
J
Hope
T
T
Esiri
M M
MM
Francis
P T
PT
Chen
C P
CP
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D003072:Cognition Disorders / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D011485:Protein Binding / Q000502:physiology; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D013702:Temporal Lobe / Q000378:metabolism* / Q000473:pathology
D044402:Receptor, Serotonin, 5-HT2A