Laura Michiels1, Aline Delva2, June van Aalst3, Jenny Ceccarini3, Wim Vandenberghe2, Mathieu Vandenbulcke4, Michel Koole3, Robin Lemmens5, Koen Van Laere6. 1. Department of Neurosciences, KU Leuven, Belgium; VIB, Center for Brain & Disease Research, Laboratory of Neurobiology, Belgium; Department of Neurology, University Hospitals Leuven, Belgium. Electronic address: laura.michiels@uzleuven.be. 2. Department of Neurosciences, KU Leuven, Belgium; Department of Neurology, University Hospitals Leuven, Belgium. 3. Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, KU Leuven, Belgium. 4. VIB, Center for Brain & Disease Research, Laboratory of Neurobiology, Belgium; Department of Geriatric Psychiatry, University Psychiatric Centre, KU Leuven, Belgium. 5. Department of Neurosciences, KU Leuven, Belgium; VIB, Center for Brain & Disease Research, Laboratory of Neurobiology, Belgium; Department of Neurology, University Hospitals Leuven, Belgium. 6. Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, KU Leuven, Belgium; Division of Nuclear Medicine, University Hospitals Leuven, Belgium.
Abstract
RATIONALE: 11C-UCB-J binds to synaptic vesicle glycoprotein 2A, a protein ubiquitously expressed in presynaptic nerve terminals, and can therefore serve as in vivo proxy of synaptic density. There are discrepancies in postmortem data on stability of synaptic density with healthy aging. In this study, healthy aging and sex as potential modifiers of 11C-UCB-J binding were investigated in healthy volunteers over 7 adult decades, assuming that the number of SV2A vesicles per synapse is not influenced by age or sex. METHODS: 80 healthy volunteers underwent 11C-UCB-J PET and structural T1 and T2 MR imaging. Grey matter changes with aging were firstly evaluated by voxel-based morphometry (VBM). Parametric 11C-UCB-J standardized uptake value ratio (SUVR) images were calculated using the centrum semiovale as reference tissue. To correct for atrophy-related partial volume effects, a region-based voxel-wise type partial volume correction (PVC) was applied in FreeSurfer. The correlations of 11C-UCB-J binding with age and with sex were investigated by a voxel-based and volume-of-interest (VOI)-based approach, and with and without PVC to assess the contribution of underlying morphology changes upon aging. RESULTS: Full results were available for 78 participants (19-85y; 33 M/45 F). VBM grey matter concentration changes with aging were most predominant in the perisylvian and frontal regions. After PVC, no significantly decreased 11C-UCB-J SUVR with aging was found in the voxel-based analysis, whereas the VOI-based analysis showed a slight decrease in the caudate nucleus (-1.7% decrease per decade, p= 0.0025) only. There was no association between sex and 11C-UCB-J SUVR, nor an interaction between aging and sex for this parameter. CONCLUSION: In vivo, PET using 11C-UCB-J does not support a cortical decrease of synaptic density with aging, whereas subcortically a small effect with aging in the caudate nucleus was observed. In addition, no association between synaptic density and sex was detected, which allows pooling of datasets of both sexes.
RATIONALE: 11C-UCB-J binds to synaptic vesicle glycoprotein 2A, a protein ubiquitously expressed in presynaptic nerve terminals, and can therefore serve as in vivo proxy of synaptic density. There are discrepancies in postmortem data on stability of synaptic density with healthy aging. In this study, healthy aging and sex as potential modifiers of 11C-UCB-J binding were investigated in healthy volunteers over 7 adult decades, assuming that the number of SV2A vesicles per synapse is not influenced by age or sex. METHODS: 80 healthy volunteers underwent 11C-UCB-J PET and structural T1 and T2 MR imaging. Grey matter changes with aging were firstly evaluated by voxel-based morphometry (VBM). Parametric 11C-UCB-J standardized uptake value ratio (SUVR) images were calculated using the centrum semiovale as reference tissue. To correct for atrophy-related partial volume effects, a region-based voxel-wise type partial volume correction (PVC) was applied in FreeSurfer. The correlations of 11C-UCB-J binding with age and with sex were investigated by a voxel-based and volume-of-interest (VOI)-based approach, and with and without PVC to assess the contribution of underlying morphology changes upon aging. RESULTS: Full results were available for 78 participants (19-85y; 33 M/45 F). VBM grey matter concentration changes with aging were most predominant in the perisylvian and frontal regions. After PVC, no significantly decreased 11C-UCB-J SUVR with aging was found in the voxel-based analysis, whereas the VOI-based analysis showed a slight decrease in the caudate nucleus (-1.7% decrease per decade, p= 0.0025) only. There was no association between sex and 11C-UCB-J SUVR, nor an interaction between aging and sex for this parameter. CONCLUSION: In vivo, PET using 11C-UCB-J does not support a cortical decrease of synaptic density with aging, whereas subcortically a small effect with aging in the caudate nucleus was observed. In addition, no association between synaptic density and sex was detected, which allows pooling of datasets of both sexes.
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