title: 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.
authors.affiliation: Nuclear Medicine and Molecular Imaging, University Hospitals Leuven, Belgium; Department of Imaging & Pathology, KU Leuven, Belgium. Electronic address: rawaha.ahmad@uzleuven.be.
authors.forename: Rawaha
authors.initials: R
authors.lastname: Ahmad
authors.affiliation: Nuclear Medicine and Molecular Imaging, University Hospitals Leuven, Belgium; Department of Imaging & Pathology, KU Leuven, Belgium.
authors.forename: Karolien
authors.initials: K
authors.lastname: Goffin
authors.affiliation: Department of Old Age Psychiatry, University Hospitals Leuven, Belgium; Department of Neurosciences, KU Leuven, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Van den Stock
authors.affiliation: Department of Old Age Psychiatry, University Hospitals Leuven, Belgium; Department of Neurosciences, KU Leuven, Belgium.
authors.forename: François-Laurent
authors.initials: FL
authors.lastname: De Winter
authors.affiliation: Nuclear Medicine and Molecular Imaging, University Hospitals Leuven, Belgium; Department of Imaging & Pathology, KU Leuven, Belgium.
authors.forename: Evy
authors.initials: E
authors.lastname: Cleeren
authors.affiliation: Laboratory for Radiopharmacy, KU Leuven, Belgium.
authors.forename: Guy
authors.initials: G
authors.lastname: Bormans
authors.affiliation: Geriatric Medicine, University Hospitals Leuven, Belgium; Department of Clinical and Experimental Medicine, KU Leuven, Belgium.
authors.forename: Jos
authors.initials: J
authors.lastname: Tournoy
authors.affiliation: Department of Old Age Psychiatry, University Hospitals Leuven, Belgium; Department of Neurosciences, KU Leuven, Belgium.
authors.forename: Philippe
authors.initials: P
authors.lastname: Persoons
authors.affiliation: Nuclear Medicine and Molecular Imaging, University Hospitals Leuven, Belgium; Department of Imaging & Pathology, KU Leuven, Belgium.
authors.forename: Koen
authors.initials: K
authors.lastname: Van Laere
authors.affiliation: Department of Old Age Psychiatry, University Hospitals Leuven, Belgium; Department of Neurosciences, KU Leuven, Belgium.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Vandenbulcke
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000814:Aniline Compounds; D001057:Apolipoproteins E / Q000235:genetics; D052160:Benzothiazoles; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D003071:Cognition / Q000502:physiology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D011725:Pyridines; D019275:Radiopharmaceuticals; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D001057:Apolipoproteins E; D052160:Benzothiazoles; C571130:CNR1 protein, human; C528731:MK-9470; D011725:Pyridines; D019275:Radiopharmaceuticals; D043884:Receptor, Cannabinoid, CB1; D013844:Thiazoles
keywords: Alzheimer's disease; Amyloid; ApoE; Cannabinoid receptor; MMSE; PET scan