Loss of serotonin 2A receptors exceeds loss of serotonergic projections in early Alzheimer's disease: a combined [11C]DASB and [18F]altanserin-PET study.

Abstract

In patients with Alzheimer's disease (AD), postmortem and imaging studies have revealed early and prominent reductions in cerebral serotonin 2A (5-HT(2A)) receptors. To establish if this was due to a selective disease process of the serotonin system, we investigated the cerebral 5-HT(2A) receptor and the serotonin transporter binding, the latter as a measure of serotonergic projections and neurons. Twelve patients with AD (average Mini Mental State Examination [MMSE]: 24) and 11 healthy age-matched subjects underwent positron emission tomography (PET) scanning with [(18)F]altanserin and [(11)C]N,N-Dimethyl-2-(2-amino-4-cyanopheylthio)benzylamine ([(11)C]DASB). Overall [(18)F]altanserin binding was markedly reduced in AD by 28%-39% (p = 0.02), whereas the reductions in [(11)C]DASB binding were less prominent and mostly insignificant, except for a marked reduction of 33% in mesial temporal cortex (p = .0005). No change in [(11)C]DASB binding was found in the midbrain. We conclude that the prominent reduction in neocortical 5-HT(2A) receptor binding in early AD is not caused by a primary loss of serotonergic neurons or their projections.

• Authors: Lisbeth Marner, Vibe G Frokjaer, Jan Kalbitzer, Szabolcs Lehel, Karine Madsen, William F C Baaré, Gitte M Knudsen, Steen G Hasselbalch
• Journal: Neurobiology of aging (Neurobiol Aging) Vol. 33 Issue 3 Pg. 479-87 (Mar 2012) ISSN: 1558-1497 [Electronic] United States
• PMID: 20510480 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Benzylamines
• Carbon Radioisotopes
• Fluorine Radioisotopes
• N,N-dimethyl-2-(2-amino-4-cyanophenylthio)benzylamine
• Receptor, Serotonin, 5-HT2A
• altanserin
• Ketanserin

Topics

• Aged
• Aged, 80 and over
• Alzheimer Disease (diagnostic imaging, metabolism, pathology)
• Benzylamines
• Carbon Radioisotopes
• Cerebral Cortex (diagnostic imaging, metabolism, pathology)
• Female
• Fluorine Radioisotopes
• Humans
• Ketanserin (analogs & derivatives)
• Male
• Neural Pathways (diagnostic imaging, metabolism, pathology)
• Positron-Emission Tomography (methods)
• Raphe Nuclei (diagnostic imaging, metabolism, pathology)
• Receptor, Serotonin, 5-HT2A (deficiency, metabolism)
• Serotonergic Neurons (diagnostic imaging, metabolism, pathology)