Brain Structure and Function

, Volume 221, Issue 3, pp 1387–1402 | Cite as

In vivo characterization of metabotropic glutamate receptor type 5 abnormalities in behavioral variant FTD

  • Antoine Leuzy
  • Eduardo Rigon Zimmer
  • Jonathan Dubois
  • Jens Pruessner
  • Cory Cooperman
  • Jean-Paul Soucy
  • Alexey Kostikov
  • Esther Schirmaccher
  • René Désautels
  • Serge Gauthier
  • Pedro Rosa-NetoEmail author
Original Article


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 ([11C]ABP688) in a sample of bvFTD patients. In addition, we sought to determine the overlap between availability of mGluR5 and neurodegeneration, as measured using [18F]FDG-PET and voxel-based morphometry (VBM). Availability of mGluR5 and glucose metabolism ([18F]FDG) were measured in bvFTD (n = 5) and cognitively normal (CN) subjects (n = 10). [11C]ABP688 binding potential maps (BPND) were calculated using the cerebellum as a reference region, with [18F]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 [11C]ABP688 BPND throughout frontal, temporal and subcortical areas. These areas were likewise characterized by significant hypometabolism and GM loss, with overlap between reduced [11C]ABP688 BPND and hypometabolism superior to that for GM atrophy. Several regions were characterized only by decreased binding of [11C]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 [11C]ABP688 may prove a suitable marker of glutamatergic neurotransmission in vivo.


Behavioral variant frontotemporal dementia Frontotemporal lobar degeneration Positron emission tomography 11C-ABP688 Metabotropic glutamate receptor type 5 Excitotoxicity 



The authors wish to thank the patients and their families for participating in this study. This work was supported by the Canadian Institutes of Health Research (CIHR) [MOP-11-51-31], the Alan Tiffin Foundation, the Alzheimer’s Association [NIRG-08-92090], and the Fonds de la recherche en santé du Québec (Chercheur boursier). The authors wish to acknowledge the help of the imaging staff at the Montreal Neurological Institute McConnell Brain Imaging Centre, including Reda Bouhachi, Simion Matei, Rick Fukasawa (PET Technologists), Ron Lopez, David Costa, Louise Marcotte (MRI Technologists), and André Cormier (Chief MRI Technologist).

Conflict of interest

The authors declare no conflict of interest.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Antoine Leuzy
    • 1
    • 2
  • Eduardo Rigon Zimmer
    • 1
    • 2
    • 3
  • Jonathan Dubois
    • 4
  • Jens Pruessner
    • 5
    • 6
  • Cory Cooperman
    • 6
    • 7
  • Jean-Paul Soucy
    • 8
  • Alexey Kostikov
    • 8
  • Esther Schirmaccher
    • 8
  • René Désautels
    • 9
  • Serge Gauthier
    • 2
  • Pedro Rosa-Neto
    • 1
    • 2
    Email author
  1. 1.Translational Neuroimaging LaboratoryMcGill Centre for Studies in Aging, McGill UniversityMontrealCanada
  2. 2.Alzheimer’s Disease Research Unit McGill Centre for Studies in Aging, McGill UniversityMontrealCanada
  3. 3.Department of BiochemistryFederal University of Rio Grande do SulPorto AlegreBrazil
  4. 4.Department of Neurology and NeurosurgeryMontreal Neurological Institute, McGill UniversityMontrealCanada
  5. 5.McGill Centre for Studies in Aging, McGill UniversityMontrealCanada
  6. 6.Department of PsychiatryDouglas Mental Health University Institute, McGill UniversityMontrealCanada
  7. 7.Department of PsychologyMcGill UniversityMontrealCanada
  8. 8.McConnell Brain Imaging CentreMontreal Neurological Institute, McGill UniversityMontrealCanada
  9. 9.Division of Geriatric PsychiatryDouglas Mental Health University InstituteMontrealCanada

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