Differential involvement of hippocampal serotonin1A receptors and re-uptake sites in non-cognitive behaviors of Alzheimer's disease.
BACKGROUND
Previous studies have shown extensive serotonergic deficits in the hippocampus of Alzheimer's disease (AD) patients. However, it is unclear whether such deficits play a role in non-cognitive, neuropsychiatric behaviors that occur frequently in AD and cause significant caregiver distress.


OBJECTIVE
In this study, we aimed to correlate serotonergic markers in the AD hippocampus with neuropsychiatric behaviors.


METHODS
Using postmortem hippocampal homogenates from aged controls as well as a cohort of longitudinally assessed AD patients, measurements of 5-HT(1A) receptors, 5-HT(2A) receptors, and serotonin re-uptake (5-HTT) sites were performed by binding with (3)H-labeled 8-OH-DPAT, ketanserin, and citalopram, respectively.


RESULTS
Alterations of 5-HT(1A) receptors and 5-HTT were found to be differentially involved in neuropsychiatric behaviors, with loss of 5-HT(1A) receptors specifically correlated with depressive symptoms, while 5-HTT sites were preserved or up-regulated in patients with aggressive behaviors.


CONCLUSIONS
Our data suggest that neuropsychiatric behaviors in AD share certain neurochemical features with psychiatric disorders like major depression and that serotonergic drugs used in psychiatric disorders may also be efficacious against behavioral symptoms in AD.
Lai
Mitchell K P
MK
Memory, Aging and Cognition Centre, National University Health System, Kent Ridge, Singapore. mitchell.lai@dementia-research.org
Tsang
Shirley W
SW
Esiri
Margaret M
MM
Francis
Paul T
PT
Wong
Peter T-H
PT
Chen
Christopher P
CP
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000503:physiopathology*; D001344:Autopsy; D001665:Binding Sites; D015283:Citalopram / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D007650:Ketanserin / Q000378:metabolism; D008137:Longitudinal Studies; D008297:Male; D011446:Prospective Studies; D011485:Protein Binding; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*
D015283:Citalopram; D044282:Receptor, Serotonin, 5-HT1A; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D007650:Ketanserin