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Published May 18, 2018 | Version v1
Journal article Open

[18F]FMPEP-d2 PET imaging shows age- and genotype-dependent impairments in the availability of cannabinoid receptor 1 in a mouse model of Alzheimer's disease.

  • 1. MediCity Research Laboratory, University of Turku, Turku, Finland; PET Preclinical Laboratory, Turku PET Centre, University of Turku, Turku, Finland and Doctoral Programme in Clinical Research, University of Turku, Turku, Finland
  • 2. MediCity Research Laboratory, University of Turku, Turku, Finland and PET Preclinical Laboratory, Turku PET Centre, University of Turku, Turku, Finland
  • 3. Radiopharmaceutical Chemistry Laboratory, Turku PET Centre, University of Turku, Turku, Finland
  • 4. MediCity Research Laboratory, University of Turku, Turku, Finland and Institute of Biomedicine, University of Turku, Turku, Finland
  • 5. The Department of Biostatistics, University of Turku, Turku, Finland
  • 6. Radiopharmaceutical Chemistry Laboratory, Turku PET Centre, University of Turku, Turku, Finland; Accelerator Laboratory, Turku PET Centre, Åbo Akademi University, Turku, Finland and Department of Chemistry, University of Turku, Turku, Finland
  • 7. Turku PET Centre, Turku University Hospital, Turku, Finland and Division of Clinical Neurosciences, Turku University Hospital, Turku, Finland

Description

Abstract

Contradictory findings on the role of the type 1 cannabinoid receptor (CB1R) during the pathogenesis of Alzheimer’s disease (AD) have been reported. Here, we evaluated the CB1R brain profile in an AD mouse model using longitudinal positron emission tomography with an inverse agonist for CB1R, [18F]FMPEP-d2. APP/PS1-21 and wild-type (n 1⁄4 8 in each group) mice were repeatedly imaged between 6 to 15 months of age, accompanied by brain autoradiography, western blot, and CB1R immunohistochemistry with additional mice. [18F]FMPEP-d2 positron emission tomography demonstrated lower (p < 0.05) binding ratios in the parietotemporal cortex and hippocampus of APP/PS1-21 mice compared with age-matched wild-type mice. Western blot demonstrated no differences between APP/PS1-21 and wild-type mice in the CB1R abundance, whereas significantly lower (p < 0.05) receptor expression was observed in male than female mice. The results provide the first demonstration that [18F]FMPEP-d2 is a promising imaging tool for AD research in terms of CB1R availability, but not expression. This finding may further facilitate the development of novel therapeutic approaches based on endocannabinoid regulation.

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Funding

INMIND – Imaging of Neuroinflammation in Neurodegenerative Diseases 278850
European Commission