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

Abstract

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.

Keywords: Alzheimer's disease; Amyloid; ApoE; Cannabinoid receptor; MMSE; PET scan.