A distinct [ 18 F]MPPF PET profile in amnestic mild cognitive impairment compared to mild Alzheimer's disease L. Truchot, a,b,c,d, ⁎ ,1 N. Costes, b,c L. Zimmer, a,b,c B. Laurent, e,f D. Le Bars, a,b C. Thomas-Antérion, e,f B. Mercier, a,d M. Hermier, a A. Vighetto, a,c,d and P. Krolak-Salmon a,c,d a University Lyon 1 and Hospices Civils de Lyon, Hôpital Neurologique, 69677 Bron cedex, France b CERMEP-Imagerie du vivant, 59 boulevard Pinel, 69003 Lyon, France c Institut Fédératif des Neurosciences de Lyon, 59 boulevard Pinel, 69394 Lyon Cedex 03, France d Memory Research Resource Centre for Alzheimer's Disease of Lyon, France e Hôpital Bellevue, Service de Neurologie, 25 boulevard Pasteur, 42100 Saint Etienne, France f Memory Research Resource Centre for Alzheimer's Disease of Saint Etienne, France Received 14 May 2007; revised 18 November 2007; accepted 8 January 2008 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 compen- satory 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. © 2008 Published by Elsevier Inc. Introduction The earliest and most severe cognitive deficit in Alzheimer's disease (AD) concerns episodic memory (Dubois et al., 2007). Pathologically, neurofibrillary tangles first appear in the rhinal cortex, then in the hippocampus and finally spread into the neocortex (Braak and Braak, 1991; Delacourte et al., 1999). The recent development of selective PET ligands for 5-HT 1A receptors, including [ 18 F]MPPF, allows the in vivo exploration of the serotonergic system in human brain (Passchier et al., 2000; Aznavour and Zimmer, 2007, for a review). These serotonergic receptors are known to be numerous in the hippocampus. To date, only two studies with PET [ 18 F]MPPF have been performed in AD patients, focusing only on the hippocampus (Kepe et al., 2006; Truchot et al., 2007). These studies have shown major decreases of 5-HT 1A receptor density in the hippocampus of AD patients, but divergent results in aMCI patients. Thus the first study (Kepe et al., 2006) demonstrated a slight decrease of 5-HT 1A receptor binding in the hippocampus of aMCI patients and a dramatic decrease in AD patients compared to controls. The second study (Truchot et al., 2007) showed a large increase of 5-HT 1A receptor binding in the hippocampus of aMCI patients and a dramatic decrease in AD patients compared to controls. A likely explanation for the divergent result was based upon the fact that the second study used partial volume effect correction to compensate for hippocampus atrophy. A compensatory mechanism with an up regulation of serotonergic metabolism manifesting during the aMCI stage, a pre- dementia stage of AD, in contrast with a breakdown during the mild YNIMG-05176; No. of pages: 6; 4C: www.elsevier.com/locate/ynimg NeuroImage xx (2008) xxx – xxx ⁎ Corresponding author. Hôpital Neurologique Pierre Wertheimer, Service de Neurologie du Pr Vighetto, 59 boulevard Pinel 69677 Bron cedex, France. Fax: +33 472688610. E-mail address: lydie.truchot@free.fr (L. Truchot). 1 Current address: Forenap Pharma, 27 Rue du 4ème RSM, 68250 Roufach, France. Available online on ScienceDirect (www.sciencedirect.com). 1053-8119/$ - see front matter © 2008 Published by Elsevier Inc. doi:10.1016/j.neuroimage.2008.01.030 ARTICLE IN PRESS Please cite this article as: Truchot, L., et al., A distinct [ 18 F]MPPF PET profile in amnestic mild cognitive impairment compared to mild Alzheimer's disease, NeuroImage (2008), doi:10.1016/j.neuroimage.2008.01.030