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Published online before print June 13, 2007, 10.1097/JGP.0b013e3180488325
Am J Geriatr Psychiatry 15:888-898, October 2007
© 2007 American Association for Geriatric Psychiatry
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Article

A Positron Emission Tomography Study of 5-Hydroxytryptamine-1A Receptors in Alzheimer Disease

Krista L. Lanctôt, Ph.D., Doug F. Hussey, B.Sc., Nathan Herrmann, M.D., FRCP(C), Sandra E. Black, M.D., FRCP(C), Pablo M. Rusjan, Ph.D., Alan A. Wilson, Ph.D., Sylvain Houle, M.D., Ph.D., FRCP(C), Nicole Kozloff, B.A., Nicholaas Paul L.G. Verhoeff, M.D., Ph.D., FRCP(C), and Shitij Kapur, M.D., Ph.D., FRCP(C)

From the Neuropharmacology Research Program and Geriatric Psychiatry (KLL, NH, NK) and the Linda C. Campbell Cognitive Neurology Research Unit, Department of Medicine (SEB), Sunnybrook Health Sciences Centre; the Departments of Psychiatry (KLL, NH, NPLGV), Pharmacology (KLL), and Medicine (NH); and the Institute of Medical Sciences (NH, SEB, NPLGV), University of Toronto; the Kunin-Lunenfeld Applied Research Unit (KLL, NPLGV) and the Rotman Research Institute (SEB, SK), Baycrest Centre for Geriatric Care; the Vivian M. Rakoff PET Imaging Centre (DFH, PMR, AAW, SH, SK); and the Schizophrenia Program, Centre for Addiction and Mental Health (SK); Toronto, Ontario, Canada.

Objective: The important role of serotonin-1A (5-hydroxytryptamine-1A [5-HT1A]) receptors in cognition, behavior, and drug response is increasingly being recognized. Postmortem studies suggest decreased 5-HT1A 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-HT1A receptor losses in mild to moderate AD.

Methods: The authors examined 5-HT1A 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-HT1A receptor radioligand, [11C]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-HT1A 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-HT1A BP in the right MTC, but not in the other ROIs.

Conclusion: Given the strategic role of these receptors, loss of right medial temporal 5-HT1A receptors might play an important role in AD symptomatology.

Key Words: Alzheimer disease • serotonin • positron emission tomography






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