Article 2019

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\textquotesingles 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 \textequals 70.03 $\pm$ 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\textquoteright (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.}

Author(s): Quevenco, FC and Schreiner, SJ and Preti, MG and van Bergen, JMG and Kirchner, T and Wyss, M and Steininger, SC and Gietl, A and Leh, SE and Buck, A and Pruessmann, KP and Hock, C and Nitsch, RM and Henning, A and Van De Ville, D and Unschuld, PG
Journal: {NeuroImage: Clinical}
Volume: 22
Pages: 1--10
Year: 2019
Publisher: Elsevier
Bibtex Type: Article (article)
DOI: 10.1016/j.nicl.2019.101776
Electronic Archiving: grant_archive

BibTex

@article{item_3047124,
  title = {{GABA and glutamate moderate beta-amyloid related functional connectivity in cognitively unimpaired old-aged adults}},
  journal = {{NeuroImage: Clinical}},
  abstract = {{Background Effects of beta-amyloid accumulation on neuronal function precede the clinical manifestation of Alzheimer\textquotesingles 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 \textequals 70.03 $\pm$ 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\textquoteright (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.}},
  volume = {22},
  pages = {1--10},
  publisher = {Elsevier},
  year = {2019},
  slug = {item_3047124},
  author = {Quevenco, FC and Schreiner, SJ and Preti, MG and van Bergen, JMG and Kirchner, T and Wyss, M and Steininger, SC and Gietl, A and Leh, SE and Buck, A and Pruessmann, KP and Hock, C and Nitsch, RM and Henning, A and Van De Ville, D and Unschuld, PG}
}