title: Up-regulation of hippocampal serotonin metabolism in mild cognitive impairment.
abstract: OBJECTIVE
  Recent studies have suggested modifications of serotonin cerebral metabolism and of 5-HT(1A) receptors density in Alzheimer disease (AD). This study aims at exploring hippocampus 5-HT(1A) receptor density in patients at the amnesic mild cognitive impairment (aMCI) and mild AD dementia stages.
  
  
  METHODS
  With use of PET with a selective 5-HT(1A) antagonist, 2'-methoxyphenyl-(N-2'-pyridinyl)-p-[(18)F]fluoro-benzamidoethylpiperazine ([(18)F]MPPF), the hippocampus 5-HT(1A) binding potential (BP) was quantified in 10 patients with mild AD, in 11 patients with aMCI, and in 21 aged paired control subjects. To take into account hippocampal atrophy, a partial volume correction was applied to the [(18)F]MPPF data, leading to the calculation of a corrected BP (BP(c)). Comparison of hippocampus BP over populations was performed using Kruskal-Wallis rank analysis.
  
  
  RESULTS
  Hippocampus serotonergic receptor binding distinguishes patients from controls and patients with aMCI from patients with AD. In aMCI patients, the mean hippocampus BP(c) was 59% higher than the controls' (p < 0.005), and it was conversely 35% lower in patients with mild AD (p < 0.01). The difference in BP(c) values between patients with aMCI and mild AD was large, resulting in a p value of <0.0005. These differences were not related to hippocampus atrophy.
  
  
  CONCLUSIONS
  A compensatory mechanism illustrated by an up-regulation of serotonergic metabolism has been shown at the stage of amnesic mild cognitive impairment (aMCI) in contrast with a dramatic decrease at later stages of Alzheimer disease (AD). This difference of hippocampus serotonergic receptor labeling allows distinguishing of patients with aMCI from those with mild AD. Exploring 5-HT(1A) receptors with 2'-methoxyphenyl-(N-2'-pyridinyl)-p-(18)F-fluoro-benzamidoethylpiperazine PET seems to be of interest for better understanding pathophysiologic changes at early stages of AD.
authors.affiliation: Service de Neurologie D, Hôpital Neurologique, University Lyon 1, France. lydie.truchot@free.fr
authors.forename: L
authors.initials: L
authors.lastname: Truchot
authors.forename: S N
authors.initials: SN
authors.lastname: Costes
authors.forename: L
authors.initials: L
authors.lastname: Zimmer
authors.forename: B
authors.initials: B
authors.lastname: Laurent
authors.forename: D
authors.initials: D
authors.lastname: Le Bars
authors.forename: C
authors.initials: C
authors.lastname: Thomas-Antérion
authors.forename: B
authors.initials: B
authors.lastname: Croisile
authors.forename: B
authors.initials: B
authors.lastname: Mercier
authors.forename: M
authors.initials: M
authors.lastname: Hermier
authors.forename: A
authors.initials: A
authors.lastname: Vighetto
authors.forename: P
authors.initials: P
authors.lastname: Krolak-Salmon
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000523:psychology; D015415:Biomarkers / Q000378:metabolism; D003072:Cognition Disorders / Q000378:metabolism* / Q000523:psychology; D005260:Female; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography / Q000379:methods; D044282:Receptor, Serotonin, 5-HT1A / Q000096:biosynthesis / Q000378:metabolism; D012701:Serotonin / Q000096:biosynthesis / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology*