Publication

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

Dimitri Nestor Alice Van De Ville, Maria Giulia Preti
2019
Journal Articles

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 11CPittsburgh 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.

Official source

https://infoscience.epfl.ch/entities/publication/0d04e8d3-bd6b-46d7-9caf-3cd83aeafe5f

Dimitri Nestor Alice Van De Ville, Maria Giulia Preti
2019
Journal Articles

Abstract

Official source

https://infoscience.epfl.ch/entities/publication/0d04e8d3-bd6b-46d7-9caf-3cd83aeafe5f

Related concepts (32)

Frontal lobe

The frontal lobe is the largest of the four major lobes of the brain in mammals, and is located at the front of each cerebral hemisphere (in front of the parietal lobe and the temporal lobe). It is parted from the parietal lobe by a groove between tissues called the central sulcus and from the temporal lobe by a deeper groove called the lateral sulcus (Sylvian fissure). The most anterior rounded part of the frontal lobe (though not well-defined) is known as the frontal pole, one of the three poles of the cerebrum.

Parietal lobe

The parietal lobe is one of the four major lobes of the cerebral cortex in the brain of mammals. The parietal lobe is positioned above the temporal lobe and behind the frontal lobe and central sulcus. The parietal lobe integrates sensory information among various modalities, including spatial sense and navigation (proprioception), the main sensory receptive area for the sense of touch in the somatosensory cortex which is just posterior to the central sulcus in the postcentral gyrus, and the dorsal stream of the visual system.

Amyloid beta

Amyloid beta (Aβ or Abeta) denotes peptides of 36–43 amino acids that are the main component of the amyloid plaques found in the brains of people with Alzheimer's disease. The peptides derive from the amyloid-beta precursor protein (APP), which is cleaved by beta secretase and gamma secretase to yield Aβ in a cholesterol-dependent process and substrate presentation. Aβ molecules can aggregate to form flexible soluble oligomers which may exist in several forms.

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