A distinct [18F]MPPF PET profile in amnestic mild cognitive impairment compared to mild Alzheimer's disease.
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.
Truchot
L
L
University Lyon 1 and Hospices Civils de Lyon, Hôpital Neurologique, 69677 Bron cedex, France. lydie.truchot@free.fr
Costes
N
N
Zimmer
L
L
Laurent
B
B
Le Bars
D
D
Thomas-Antérion
C
C
Mercier
B
B
Hermier
M
M
Vighetto
A
A
Krolak-Salmon
P
P
D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000523:psychology; D000647:Amnesia / Q000000981:diagnostic imaging* / Q000523:psychology; D001921:Brain / Q000000981:diagnostic imaging; D003072:Cognition Disorders / Q000000981:diagnostic imaging* / Q000523:psychology; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008032:Limbic System / Q000000981:diagnostic imaging; D008297:Male; D008875:Middle Aged; D010879:Piperazines; D049268:Positron-Emission Tomography; D011725:Pyridines; D019275:Radiopharmaceuticals; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism
D010879:Piperazines; D011725:Pyridines; D019275:Radiopharmaceuticals; D044282:Receptor, Serotonin, 5-HT1A; C416325:4-(2'-methoxyphenyl)-1-(2'-(N-2'-pyridinyl)-p-(18F)fluorobenzamido )ethylpiperazine