A distinct [18F]MPPF PET profile in amnestic mild cognitive impairment compared to mild Alzheimer's disease.

Abstract

To date, two positron emission tomography (PET) studies have explored 5-HT(1A) receptor density in the hippocampus of Alzheimer's disease (AD) patients. They showed early changes of 5-HT(1A) receptors in this brain region, known to have a dense serotonergic innervation. These studies only reported measurements in hippocampus. In the present PET study, we used an antagonist of 5-HT(1A) receptors, the [(18)F]MPPF (1) to explore 5-HT(1A) receptor density in the whole brain of AD patients at a mild stage of dementia and amnestic mild cognitive impairment (aMCI) patients compared to a control population; (2) to explore more precisely the 5-HT(1A) receptor density in the limbic brain regions of AD patients and aMCI patients compared to controls. Voxel-based analyses were performed to assess differences in the [(18)F]MPPF binding potential (BP) between AD patients and aMCI patients compared to controls. Analyses of whole-brain [(18)F]MPPF BP showed a global decrease in AD brains in contrast with a global increase in aMCI brains. In AD brains, a significant decrease of BP was detected in hippocampus and parahippocampal gyrus, whereas a significant increase of BP was observed in the inferior occipital gyrus in aMCI brains. These whole brain results are in accordance to hippocampal data reported in a previous study, showing an increase of [(18)F]MPPF binding in the aMCI group contrasting with a decrease in the AD group. Altogether, these results suggest the implication of a compensatory mechanism illustrated by an up regulation of serotonergic metabolism at the aMCI stage before a breakdown of this mechanism at the AD stage. This difference of serotonergic receptor labeling allows to distinguish the groups of aMCI patients from mild AD patients with specific [(18)F]MPPF PET profiles for each patient group.

• Authors: L Truchot, N Costes, L Zimmer, B Laurent, D Le Bars, C Thomas-Antérion, B Mercier, M Hermier, A Vighetto, P Krolak-Salmon
• Journal: NeuroImage (Neuroimage) Vol. 40 Issue 3 Pg. 1251-6 (Apr 15 2008) ISSN: 1053-8119 [Print] United States
• PMID: 18313943 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Piperazines
• Pyridines
• Radiopharmaceuticals
• Receptor, Serotonin, 5-HT1A
• 4-(2'-methoxyphenyl)-1-(2'-(N-2'-pyridinyl)-p-(18F)fluorobenzamido )ethylpiperazine

Topics

• Aged
• Alzheimer Disease (diagnostic imaging, psychology)
• Amnesia (diagnostic imaging, psychology)
• Brain (diagnostic imaging)
• Cognition Disorders (diagnostic imaging, psychology)
• Female
• Functional Laterality (physiology)
• Humans
• Image Processing, Computer-Assisted
• Limbic System (diagnostic imaging)
• Male
• Middle Aged
• Piperazines
• Positron-Emission Tomography
• Pyridines
• Radiopharmaceuticals
• Receptor, Serotonin, 5-HT1A (metabolism)