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Quantification of brain cholinergic denervation in Alzheimer’s disease using PET imaging with [18F]-FEOBV

  • Molecular Psychiatry volume 22, pages 15311538 (2017)
  • doi:10.1038/mp.2017.183
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Abstract

18F-fluoroethoxybenzovesamicol (FEOBV) is a new PET radiotracer that binds to the vesicular acetylcholine transporter. In both animals and healthy humans, FEOBV was found sensitive and reliable to characterize presynaptic cholinergic nerve terminals in the brain. It has been used here for we believe the first time in patients with Alzheimer’s disease (AD) to quantify brain cholinergic losses. The sample included 12 participants evenly divided in healthy subjects and patients with AD, all assessed with the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) cognitive scales. Every participant underwent three consecutive PET imaging sessions with (1) the FEOBV as a tracer of the cholinergic terminals, (2) the 18F-NAV4694 (NAV) as an amyloid-beta tracer, and (3) the 18F-Fluorodeoxyglucose (FDG) as a brain metabolism agent. Standardized uptake value ratios (SUVRs) were computed for each tracer, and compared between the two groups using voxel wise t-tests. Correlations were also computed between each tracer and the cognitive scales, as well as between FEOBV and the two other radiotracers. Results showed major reductions of FEOBV uptake in multiple cortical areas that were evident in each AD subject, and in the AD group as a whole when compared to the control group. FDG and NAV were also able to distinguish the two groups, but with lower sensitivity than FEOBV. FEOBV uptake values were positively correlated with FDG in numerous cortical areas, and negatively correlated with NAV in some restricted areas. The MMSE and MoCA cognitive scales were found to correlate significantly with FEOBV and with FDG, but not with NAV. We concluded that PET imaging with FEOBV is more sensitive than either FDG or NAV to distinguish AD patients from control subjects, and may be useful to quantify disease severity. FEOBV can be used to assess cholinergic degeneration in human, and may represent an excellent biomarker for AD.

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Acknowledgements

Marc-André Bedard received research funding from the Canadian Institute of Health Research (CIHR), and the Fonds de Recherche du Québec—Santé (FRQ-S). We are indebted to the subjects who participated in this study. We thank the two companies ABX Advanced Biochemical Compounds (Radeberg, Germany), and Navidea Biopharmaceutical (Dublin, OH, USA) for providing us with the FEOBV and the NAV4694 precursors, respectively.

Author contributions

MAB and JPS were responsible for conception and design of the study. MA, CLD, AK, SG, PRN and PG were responsible for acquisition and analysis of data. MAB, MA, CLD and JPS were responsible for drafting the manuscript text, tables and figures.

Author information

Affiliations

  1. Université du Québec à Montréal (UQAM), Cognitive Pharmacology Research Unit, Montreal, QC, Canada

    • M Aghourian
    • , C Legault-Denis
    •  & M-A Bédard
  2. McConnell Brain Imaging Centre, Montreal Neurological Institute, Montreal, QC, Canada

    • M Aghourian
    • , C Legault-Denis
    • , J-P Soucy
    • , P Rosa-Neto
    • , A Kostikov
    • , P Gravel
    •  & M-A Bédard
  3. McGill Centre for Studies in Aging, Douglas Mental Health University Institute, Verdun, QC, Canada

    • M Aghourian
    • , C Legault-Denis
    • , P Rosa-Neto
    • , S Gauthier
    •  & M-A Bédard
  4. Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada

    • J-P Soucy
    • , P Rosa-Neto
    • , S Gauthier
    •  & A Kostikov
  5. PERFORM Centre, Concordia University, Montreal, QC, Canada

    • J-P Soucy

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Competing interests

M-AB reports personal fees from Pfizer Canada, Shire Pharma, Purdue Pharma, and Merck Canada, outside the submitted work. PRN reports personal fees from Lilly and TauRx pharmaceuticals, outside the submitted work. Serge Gauthier reports personal fees from Lilly, Merck Canada, Lundbeck, Novartis and Pfizer Canada, outside the submitted work. The remaining authors declare no conflict of interest.

Corresponding author

Correspondence to M-A Bédard.