Up-regulation of hippocampal serotonin metabolism in mild cognitive impairment.
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.
Truchot
L
L
Service de Neurologie D, Hôpital Neurologique, University Lyon 1, France. lydie.truchot@free.fr
Costes
S N
SN
Zimmer
L
L
Laurent
B
B
Le Bars
D
D
Thomas-Antérion
C
C
Croisile
B
B
Mercier
B
B
Hermier
M
M
Vighetto
A
A
Krolak-Salmon
P
P
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*