title: In vivo characterization of metabotropic glutamate receptor type 5 abnormalities in behavioral variant FTD.
abstract: Although the pathogenesis underlying behavioral variant frontotemporal dementia (bvFTD) has yet to be fully understood, glutamatergic abnormalities have been hypothesized to play an important role. The aim of the present study was to determine the availability of the metabotropic glutamate receptor type 5 (mGluR5) using a novel positron emission tomography (PET) radiopharmaceutical with high selectivity for mGluR5 ([(11)C]ABP688) in a sample of bvFTD patients. In addition, we sought to determine the overlap between availability of mGluR5 and neurodegeneration, as measured using [(18)F]FDG-PET and voxel-based morphometry (VBM). Availability of mGluR5 and glucose metabolism ([(18)F]FDG) were measured in bvFTD (n = 5) and cognitively normal (CN) subjects (n = 10). [(11)C]ABP688 binding potential maps (BPND) were calculated using the cerebellum as a reference region, with [(18)F]FDG standardized uptake ratio maps (SUVR) normalized to the pons. Grey matter (GM) concentrations were determined using VBM. Voxel-based group differences were obtained using RMINC. BvFTD patients showed widespread decrements in [(11)C]ABP688 BPND throughout frontal, temporal and subcortical areas. These areas were likewise characterized by significant hypometabolism and GM loss, with overlap between reduced [(11)C]ABP688 BPND and hypometabolism superior to that for GM atrophy. Several regions were characterized only by decreased binding of [(11)C]ABP688. The present findings represent the first in vivo report of decreased availability of mGluR5 in bvFTD. This study suggests that glutamate excitotoxicity may play a role in the pathogenesis of bvFTD and that [(11)C]ABP688 may prove a suitable marker of glutamatergic neurotransmission in vivo.
authors.affiliation: Translational Neuroimaging Laboratory, McGill Centre for Studies in Aging, McGill University, 6825 LaSalle Blvd, Montreal, QC, H4H 1R3, Canada.|Alzheimer's Disease Research Unit, McGill Centre for Studies in Aging, McGill University, Montreal, Canada.
authors.forename: Antoine
authors.initials: A
authors.lastname: Leuzy
authors.affiliation: Translational Neuroimaging Laboratory, McGill Centre for Studies in Aging, McGill University, 6825 LaSalle Blvd, Montreal, QC, H4H 1R3, Canada.|Alzheimer's Disease Research Unit, McGill Centre for Studies in Aging, McGill University, Montreal, Canada.|Department of Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Eduardo Rigon
authors.initials: ER
authors.lastname: Zimmer
authors.affiliation: Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Canada.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Dubois
authors.affiliation: McGill Centre for Studies in Aging, McGill University, Montreal, Canada.|Department of Psychiatry, Douglas Mental Health University Institute, McGill University, Montreal, Canada.
authors.forename: Jens
authors.initials: J
authors.lastname: Pruessner
authors.affiliation: Department of Psychiatry, Douglas Mental Health University Institute, McGill University, Montreal, Canada.|Department of Psychology, McGill University, Montreal, Canada.
authors.forename: Cory
authors.initials: C
authors.lastname: Cooperman
authors.affiliation: McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Canada.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Soucy
authors.affiliation: McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Canada.
authors.forename: Alexey
authors.initials: A
authors.lastname: Kostikov
authors.affiliation: McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Canada.
authors.forename: Esther
authors.initials: E
authors.lastname: Schirmaccher
authors.affiliation: Division of Geriatric Psychiatry, Douglas Mental Health University Institute, Montreal, Canada.
authors.forename: René
authors.initials: R
authors.lastname: Désautels
authors.affiliation: Alzheimer's Disease Research Unit, McGill Centre for Studies in Aging, McGill University, Montreal, Canada.
authors.forename: Serge
authors.initials: S
authors.lastname: Gauthier
authors.affiliation: Translational Neuroimaging Laboratory, McGill Centre for Studies in Aging, McGill University, 6825 LaSalle Blvd, Montreal, QC, H4H 1R3, Canada. pedro.rosa@mcgill.ca.|Alzheimer's Disease Research Unit, McGill Centre for Studies in Aging, McGill University, Montreal, Canada. pedro.rosa@mcgill.ca.
authors.forename: Pedro
authors.initials: P
authors.lastname: Rosa-Neto
mesh_terms: D000368:Aged; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002250:Carbon Radioisotopes; D005260:Female; D057180:Frontotemporal Dementia / Q000000981:diagnostic imaging / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D010091:Oximes / Q000008:administration & dosage; D049268:Positron-Emission Tomography / Q000379:methods*; D011725:Pyridines / Q000008:administration & dosage; D064529:Receptor, Metabotropic Glutamate 5 / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: C510950:3-(6-methylpyridin-2-ylethynyl)cyclohex-2-enone-O-methyloxime; D002250:Carbon Radioisotopes; C578935:GRM5 protein, human; D010091:Oximes; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D005947:Glucose
keywords: 11C-ABP688; Behavioral variant frontotemporal dementia; Excitotoxicity; Frontotemporal lobar degeneration; Metabotropic glutamate receptor type 5; Positron emission tomography