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

Quevenco, F., Schreiner, S., Preti, M., van Bergen, J., Kirchner, T., Wyss, M., et al. (2019). GABA and glutamate moderate beta-amyloid related functional connectivity in cognitively unimpaired old-aged adults. NeuroImage: Clinical, 22: 101776, pp. 1-10. doi:10.1016/j.nicl.2019.101776.

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 Creators:
Quevenco, FC, Author
Schreiner, SJ, Author
Preti, MG, Author
van Bergen, JMG, Author
Kirchner, T, Author
Wyss, M, Author
Steininger, SC, Author
Gietl, A, Author
Leh, SE, Author
Buck, A, Author
Pruessmann, KP, Author
Hock, C, Author
Nitsch, RM, Author
Henning, A1, 2, Author           
Van De Ville, D, Author
Unschuld, PG, Author
Affiliations:
1Research Group MR Spectroscopy and Ultra-High Field Methodology, Max Planck Institute for Biological Cybernetics, Max Planck Society, ou_2528692              
2Max Planck Institute for Biological Cybernetics, Max Planck Society, Spemannstrasse 38, 72076 Tübingen, DE, ou_1497794              

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 Abstract: 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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 Dates: 2019-03
 Publication Status: Issued
 Pages: -
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 Rev. Type: -
 Identifiers: DOI: 10.1016/j.nicl.2019.101776
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Title: NeuroImage: Clinical
Source Genre: Journal
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Publ. Info: Elsevier
Pages: - Volume / Issue: 22 Sequence Number: 101776 Start / End Page: 1 - 10 Identifier: ISSN: 2213-1582
CoNE: https://pure.mpg.de/cone/journals/resource/2213-1582