Regional distribution and behavioral correlates of 5-HT(2A) receptors in Alzheimer's disease with [(18)F]deuteroaltanserin and PET.
Postmortem studies show reductions in brain serotonin 2A (5-HT(2A)) receptors in Alzheimer's disease (AD). Converging evidence also suggests that serotonergic dysregulation may contribute to behavioral symptoms that frequently occur in AD. This study aimed to define regional reductions in 5-HT(2A) binding in AD patients and to examine their behavioral correlates. Nine patients with probable AD and eight elderly controls were studied using a constant infusion paradigm for equilibrium modeling of [(18)F]deuteroaltanserin with positron emission tomography (PET). Region of interest analyses were performed on PET images coregistered to MRI scans. The outcome measures BP(P) (ratio of specific brain uptake to total plasma parent concentration) and BP(ND) (ratio of specific to nondisplaceable uptake) were obtained for pertinent cortical and subcortical regions. AD patients showed a statistically significant decrease in the anterior cingulate in both BP(P) and BP(ND), but in no other region. Within the AD patient sample, no significant correlations were observed between regional 5-HT(2A) binding and behavioral measures, including depressive and psychotic symptoms. These results confirm a reduction in cortical 5-HT(2A) receptors in AD, specifically in the anterior cingulate. However, in a limited AD patient sample, they fail to demonstrate a relationship between regional 5-HT(2A) binding and major behavioral symptoms.
Santhosh
Lekshmi
L
Alzheimer's Disease Research Unit, Yale University School of Medicine, New Haven, CT 06510, USA.
Estok
Kristina M
KM
Vogel
Rebecca S
RS
Tamagnan
Gilles D
GD
Baldwin
Ronald M
RM
Mitsis
Effie M
EM
Macavoy
Martha G
MG
Staley
Julie K
JK
van Dyck
Christopher H
CH
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D000704:Analysis of Variance; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D001931:Brain Mapping; D010054:Brief Psychiatric Rating Scale; D005260:Female; D005462:Fluorine Radioisotopes / Q000378:metabolism; D006801:Humans; D007650:Ketanserin / Q000031:analogs & derivatives / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods*; D011485:Protein Binding / Q000502:physiology; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*
D005462:Fluorine Radioisotopes; D044402:Receptor, Serotonin, 5-HT2A; C071983:altanserin; D007650:Ketanserin