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

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 neur...

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Autores principales: Quevenco, F.C., Schreiner, S.J., Preti, M.G., van Bergen, J.M.G., Kirchner, T., Wyss, M., Steininger, S.C., Gietl, A., Leh, S.E., Buck, A., Pruessmann, K.P., Hock, C., Nitsch, R.M., Henning, A., Van De Ville, D., Unschuld, P.G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2019
Materias:
Regular Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6439267/
https://www.ncbi.nlm.nih.gov/pubmed/30927605
http://dx.doi.org/10.1016/j.nicl.2019.101776
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author Quevenco, F.C.
Schreiner, S.J.
Preti, M.G.
van Bergen, J.M.G.
Kirchner, T.
Wyss, M.
Steininger, S.C.
Gietl, A.
Leh, S.E.
Buck, A.
Pruessmann, K.P.
Hock, C.
Nitsch, R.M.
Henning, A.
Van De Ville, D.
Unschuld, P.G.
author_facet Quevenco, F.C.
Schreiner, S.J.
Preti, M.G.
van Bergen, J.M.G.
Kirchner, T.
Wyss, M.
Steininger, S.C.
Gietl, A.
Leh, S.E.
Buck, A.
Pruessmann, K.P.
Hock, C.
Nitsch, R.M.
Henning, A.
Van De Ville, D.
Unschuld, P.G.
author_sort Quevenco, F.C.
collection PubMed
description 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.
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spelling pubmed-64392672019-04-11 GABA and glutamate moderate beta-amyloid related functional connectivity in cognitively unimpaired old-aged adults Quevenco, F.C. Schreiner, S.J. Preti, M.G. van Bergen, J.M.G. Kirchner, T. Wyss, M. Steininger, S.C. Gietl, A. Leh, S.E. Buck, A. Pruessmann, K.P. Hock, C. Nitsch, R.M. Henning, A. Van De Ville, D. Unschuld, P.G. Neuroimage Clin Regular Article 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. Elsevier 2019-03-12 /pmc/articles/PMC6439267/ /pubmed/30927605 http://dx.doi.org/10.1016/j.nicl.2019.101776 Text en © 2019 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Regular Article
Quevenco, F.C.
Schreiner, S.J.
Preti, M.G.
van Bergen, J.M.G.
Kirchner, T.
Wyss, M.
Steininger, S.C.
Gietl, A.
Leh, S.E.
Buck, A.
Pruessmann, K.P.
Hock, C.
Nitsch, R.M.
Henning, A.
Van De Ville, D.
Unschuld, P.G.
GABA and glutamate moderate beta-amyloid related functional connectivity in cognitively unimpaired old-aged adults
title GABA and glutamate moderate beta-amyloid related functional connectivity in cognitively unimpaired old-aged adults
title_full GABA and glutamate moderate beta-amyloid related functional connectivity in cognitively unimpaired old-aged adults
title_fullStr GABA and glutamate moderate beta-amyloid related functional connectivity in cognitively unimpaired old-aged adults
title_full_unstemmed GABA and glutamate moderate beta-amyloid related functional connectivity in cognitively unimpaired old-aged adults
title_short GABA and glutamate moderate beta-amyloid related functional connectivity in cognitively unimpaired old-aged adults
title_sort gaba and glutamate moderate beta-amyloid related functional connectivity in cognitively unimpaired old-aged adults
topic Regular Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6439267/
https://www.ncbi.nlm.nih.gov/pubmed/30927605
http://dx.doi.org/10.1016/j.nicl.2019.101776
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