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

doi:10.1016/j.nicl.2019.101776

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

Research output: Contribution to journal › Article › peer-review

21 Scopus citations

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.

Original language	English (US)
Article number	101776
Journal	NeuroImage: Clinical
Volume	22
DOIs	https://doi.org/10.1016/j.nicl.2019.101776
State	Published - 2019
Externally published	Yes

Keywords

7-Tesla MRI
Alzheimer's disease
Beta-amyloid
Dynamic functional connectivity
GABA
Glutamate
Magnetic resonance spectroscopic imaging
PiB-PET

ASJC Scopus subject areas

Radiology Nuclear Medicine and imaging
Neurology
Clinical Neurology
Cognitive Neuroscience

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10.1016/j.nicl.2019.101776

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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. (2019). GABA and glutamate moderate beta-amyloid related functional connectivity in cognitively unimpaired old-aged adults. NeuroImage: Clinical, 22, Article 101776. https://doi.org/10.1016/j.nicl.2019.101776

Quevenco, FC, Schreiner, SJ, Preti, MG, van Bergen, JMG, Kirchner, T, Wyss, M, Steininger, SC, Gietl, A, Leh, SE, Buck, A, Pruessmann, KP, Hock, C, Nitsch, RM, Henning, A, Van De Ville, D & Unschuld, PG 2019, 'GABA and glutamate moderate beta-amyloid related functional connectivity in cognitively unimpaired old-aged adults', NeuroImage: Clinical, vol. 22, 101776. https://doi.org/10.1016/j.nicl.2019.101776

@article{21758f78067849ee90e7696d906eea76,

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

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{\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.",

keywords = "7-Tesla MRI, Alzheimer's disease, Beta-amyloid, Dynamic functional connectivity, GABA, Glutamate, Magnetic resonance spectroscopic imaging, PiB-PET",

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

note = "Publisher Copyright: {\textcopyright} 2019 The Authors",

year = "2019",

doi = "10.1016/j.nicl.2019.101776",

language = "English (US)",

volume = "22",

journal = "NeuroImage: Clinical",

issn = "2213-1582",

publisher = "Elsevier BV",

}

TY - JOUR

T1 - GABA and glutamate moderate beta-amyloid related functional connectivity in cognitively unimpaired old-aged adults

AU - Quevenco, F. C.

AU - Schreiner, S. J.

AU - Preti, M. G.

AU - van Bergen, J. M.G.

AU - Kirchner, T.

AU - Wyss, M.

AU - Steininger, S. C.

AU - Gietl, A.

AU - Leh, S. E.

AU - Buck, A.

AU - Pruessmann, K. P.

AU - Hock, C.

AU - Nitsch, R. M.

AU - Henning, A.

AU - Van De Ville, D.

AU - Unschuld, P. G.

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

KW - 7-Tesla MRI

KW - Alzheimer's disease

KW - Beta-amyloid

KW - Dynamic functional connectivity

KW - GABA

KW - Glutamate

KW - Magnetic resonance spectroscopic imaging

KW - PiB-PET

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UR - http://www.scopus.com/inward/citedby.url?scp=85063396167&partnerID=8YFLogxK

U2 - 10.1016/j.nicl.2019.101776

DO - 10.1016/j.nicl.2019.101776

M3 - Article

C2 - 30927605

AN - SCOPUS:85063396167

SN - 2213-1582

VL - 22

JO - NeuroImage: Clinical

JF - NeuroImage: Clinical

M1 - 101776

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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