[ 18 F]FMPEP-d 2 PET imaging shows age- and genotype-dependent impairments in the availability of cannabinoid receptor 1 in a mouse model of Alzheimer's disease

Contradictory findings on the role of the type 1 cannabinoid receptor (CB R) during the pathogenesis of Alzheimer's disease (AD) have been reported. Here, we evaluated the CB R brain profile in an AD mouse model using longitudinal positron emission tomography with an inverse agonist for CB R, [ F]FMPEP-d . APP/PS1-21 and wild-type (n = 8 in each group) mice were repeatedly imaged between 6 to 15 months of age, accompanied by brain autoradiography, western blot, and CB R immunohistochemistry with additional mice. [ F]FMPEP-d 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 CB R abundance, whereas significantly lower (p < 0.05) receptor expression was observed in male than female mice. The results provide the first demonstration that [ F]FMPEP-d is a promising imaging tool for AD research in terms of CB R availability, but not expression. This finding may further facilitate the development of novel therapeutic approaches based on endocannabinoid regulation.