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-HT1A receptor density in the hippocampus of Alzheimer's disease (AD) patients. They showed early changes of 5-HT1A 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-HT1A receptors, the [18F]MPPF (1) to explore 5-HT1A 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-HT1A 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 [18F]MPPF binding potential (BP) between AD patients and aMCI patients compared to controls. Analyses of whole-brain [18F]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 [18F]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 [18F]MPPF PET profiles for each patient group.