GABA and glutamate moderate beta-amyloid related functional connectivity in cognitively unimpaired old-aged adults

F.C. Quevenco; S.J. Schreiner; M.G. Preti; J.M.G. van Bergen; T. Kirchner; M. Wyss; S.C. Steininger; A. Gietl; S.E. Leh; A. Buck; K.P. Pruessmann; C. Hock; R.M. Nitsch; A. Henning; D. Van De Ville; P.G. Unschuld

NeuroImage: Clinical (Jan 2019)

GABA and glutamate moderate beta-amyloid related functional connectivity in cognitively unimpaired old-aged adults

F.C. Quevenco,
S.J. Schreiner,
M.G. Preti,
J.M.G. van Bergen,
T. Kirchner,
M. Wyss,
S.C. Steininger,
A. Gietl,
S.E. Leh,
A. Buck,
K.P. Pruessmann,
C. Hock,
R.M. Nitsch,
A. Henning,
D. Van De Ville,
P.G. Unschuld

Affiliations

F.C. Quevenco: Institute for Regenerative Medicine (IREM), University of Zurich, Zurich, Switzerland
S.J. Schreiner: Institute for Regenerative Medicine (IREM), University of Zurich, Zurich, Switzerland; Hospital for Psychogeriatric Medicine, Psychiatric University Hospital Zurich (PUK), Zurich, Switzerland
M.G. Preti: Department of Radiology and Medical Informatics, Université de Genève, Switzerland; Institute of Bioengineering, École polytechnique fédérale de Lausanne, Switzerland
J.M.G. van Bergen: Institute for Regenerative Medicine (IREM), University of Zurich, Zurich, Switzerland
T. Kirchner: Institute for Biomedical Engineering, University of Zurich and ETH Zurich, Zurich, Switzerland
M. Wyss: Institute for Biomedical Engineering, University of Zurich and ETH Zurich, Zurich, Switzerland
S.C. Steininger: Institute for Regenerative Medicine (IREM), University of Zurich, Zurich, Switzerland; Hospital for Psychogeriatric Medicine, Psychiatric University Hospital Zurich (PUK), Zurich, Switzerland
A. Gietl: Institute for Regenerative Medicine (IREM), University of Zurich, Zurich, Switzerland
S.E. Leh: Institute for Regenerative Medicine (IREM), University of Zurich, Zurich, Switzerland; Hospital for Psychogeriatric Medicine, Psychiatric University Hospital Zurich (PUK), Zurich, Switzerland
A. Buck: Division of Nuclear Medicine, University Hospital Zurich (USZ), Zurich, Switzerland
K.P. Pruessmann: Institute for Biomedical Engineering, University of Zurich and ETH Zurich, Zurich, Switzerland; Neuroscience Center Zurich (ZNZ), Zurich, Switzerland
C. Hock: Institute for Regenerative Medicine (IREM), University of Zurich, Zurich, Switzerland; Hospital for Psychogeriatric Medicine, Psychiatric University Hospital Zurich (PUK), Zurich, Switzerland; Neuroscience Center Zurich (ZNZ), Zurich, Switzerland
R.M. Nitsch: Institute for Regenerative Medicine (IREM), University of Zurich, Zurich, Switzerland; Hospital for Psychogeriatric Medicine, Psychiatric University Hospital Zurich (PUK), Zurich, Switzerland; Neuroscience Center Zurich (ZNZ), Zurich, Switzerland
A. Henning: Institute for Biomedical Engineering, University of Zurich and ETH Zurich, Zurich, Switzerland; Max Planck Institute for Biological Cybernetics, Tubingen, Germany
D. Van De Ville: Department of Radiology and Medical Informatics, Université de Genève, Switzerland; Institute of Bioengineering, École polytechnique fédérale de Lausanne, Switzerland
P.G. Unschuld: Institute for Regenerative Medicine (IREM), University of Zurich, Zurich, Switzerland; Hospital for Psychogeriatric Medicine, Psychiatric University Hospital Zurich (PUK), Zurich, Switzerland; Neuroscience Center Zurich (ZNZ), Zurich, Switzerland; Corresponding author at: Hospital for Psychogeriatric Medicine, PUK, Minervastrasse 145, Zurich 8032, Switzerland.

Journal volume & issue: Vol. 22

Abstract

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Background: Effects of beta-amyloid accumulation on neuronal function precede the clinical manifestation of Alzheimer's disease (AD) by years and affect distinct cognitive brain networks. As previous studies suggest a link between beta-amyloid and dysregulation of excitatory and inhibitory neurotransmitters, we aimed to investigate the impact of GABA and glutamate on beta-amyloid related functional connectivity. Methods: 29 cognitively unimpaired old-aged adults (age = 70.03 ± 5.77 years) were administered 11C-Pittsburgh Compound B (PiB) positron-emission tomography (PET), and MRI at 7 Tesla (7T) including blood oxygen level dependent (BOLD) functional MRI (fMRI) at rest for measuring static and dynamic functional connectivity. An advanced 7T MR spectroscopic imaging (MRSI) sequence based on the free induction decay acquisition localized by outer volume suppression’ (FIDLOVS) technology was used for gray matter specific measures of GABA and glutamate in the posterior cingulate and precuneus (PCP) region. Results: GABA and glutamate MR-spectra indicated significantly higher levels in gray matter than in white matter. A global effect of beta-amyloid on functional connectivity in the frontal, occipital and inferior temporal lobes was observable. Interactive effects of beta-amyloid with gray matter GABA displayed positive PCP connectivity to the frontomedial regions, and the interaction of beta-amyloid with gray matter glutamate indicated positive PCP connectivity to frontal and cerebellar regions. Furthermore, decreased whole-brain but increased fronto-occipital and temporo-parietal dynamic connectivity was found, when GABA interacted with regional beta-amyloid deposits in the amygdala, frontal lobe, hippocampus, insula and striatum. Conclusions: GABA, and less so glutamate, may moderate beta-amyloid related functional connectivity. Additional research is needed to better characterize their interaction and potential impact on AD. Keywords: Dynamic functional connectivity, 7-Tesla MRI, Alzheimer's disease, Magnetic resonance spectroscopic imaging, PiB-PET, Beta-amyloid, GABA, Glutamate

Published in NeuroImage: Clinical

ISSN: 2213-1582 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General): Computer applications to medicine. Medical informatics; Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry: Neurology. Diseases of the nervous system
Website: http://www.journals.elsevier.com/neuroimage-clinical/

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