In vivo type 1 cannabinoid receptor availability in Alzheimer's disease

The endocannabinoid system (ECS) is an important modulatory and potentially neuroprotective homeostatic system in the brain. In Alzheimer's disease (AD), the role of type 1 cannabinoid receptor (CB₁R) is unclear, with contradictory findings in post-mortem studies showing upregulation, downregulation or unchanged CB₁R status. We have investigated CB₁R availability in vivo in patients with AD, in relation to amyloid deposition, cognitive functioning and apolipoprotein E (ApoE) genotype. Eleven AD patients and 7 healthy volunteers (HV) underwent combined [¹⁸F]MK-9470 PET and [¹¹C]PIB PET scans to assess CB₁R availability and amyloid deposition, respectively, and T1 volumetric MRI for partial volume correction. We found no difference in CB₁R availability between AD and HV, VOI-based fractional uptake values (FUR) were 0.043±0.01 for AD and 0.045±0.01 for controls (p=0.9). CB₁R availability did not correlate with neuropsychological test scores and was not modulated by ApoE genotype. As expected, global [¹¹C]PIB SUVR (standardized uptake value ratio) was increased in AD (SUVR 1.9±0.3) compared to HV (1.2±0.1) with p<0.001, but no correlation was found between amyloid β (Aβ) deposition and CB₁R availability. In conclusion, we found no in vivo evidence for a difference in CB₁R availability in AD compared to age-matched controls. Taken together with recently reported in vivo CB₁R changes in Parkinson's and Huntington's disease, these data suggest that the CB₁R is differentially involved in neurodegenerative disorders.