A positron emission tomography study of 5-hydroxytryptamine-1A receptors in Alzheimer disease.
OBJECTIVE
The important role of serotonin-1A (5-hydroxytryptamine-1A [5-HT(1A)]) receptors in cognition, behavior, and drug response is increasingly being recognized. Postmortem studies suggest decreased 5-HT(1A) receptors in patients with Alzheimer disease (AD), but this has not been confirmed in vivo. Our primary objective was to assess the extent of 5-HT(1A) receptor losses in mild to moderate AD.


METHODS
The authors examined 5-HT(1A) receptors in 10 patients with mild to moderate AD and 10 healthy volunteers with the same sex and similar age using positron emission tomography imaging with the selective 5-HT(1A) receptor radioligand, [(11)C]WAY-100635. Regions of interest (ROIs) were manually drawn on coregistered magnetic resonance images for the frontal, lateral temporal, medial temporal (MTC), parietal, and cerebellar cortices. Using the simplified reference tissue model, 5-HT(1A) binding potentials (BPs) were calculated relative to the cerebellum.


RESULTS
After adjusting for partial volume effects, ROI analysis showed a significant group effect (AD versus comparison group) on BP. Analysis of between-subjects factors showed significantly decreased 5-HT(1A) BP in the right MTC, but not in the other ROIs.


CONCLUSIONS
Given the strategic role of these receptors, loss of right medial temporal 5-HT(1A) receptors might play an important role in AD symptomatology.
Lanctôt
Krista L
KL
Neuropharmacology Research Program and Geriatric Psychiatry, Toronto, Ontario, Canada. Krista.Lanctot@sunnybrook.ca
Hussey
Doug F
DF
Herrmann
Nathan
N
Black
Sandra E
SE
Rusjan
Pablo M
PM
Wilson
Alan A
AA
Houle
Sylvain
S
Kozloff
Nicole
N
Verhoeff
Nicholaas Paul L G
NP
Kapur
Shitij
S
D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002525:Cerebellar Cortex / Q000000981:diagnostic imaging* / Q000378:metabolism*; D002540:Cerebral Cortex / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000706:statistics & numerical data; D008297:Male; D010879:Piperazines; D049268:Positron-Emission Tomography / Q000706:statistics & numerical data*; D011569:Psychiatric Status Rating Scales; D011725:Pyridines; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D012720:Severity of Illness Index; D013702:Temporal Lobe / Q000000981:diagnostic imaging / Q000378:metabolism
D002250:Carbon Radioisotopes; D010879:Piperazines; D011725:Pyridines; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide