Towards a Better Understanding of GABAergic Remodeling in Alzheimer’s Disease
Open accessAbstract
γ-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the vertebrate brain. In the past, there has been a major research drive focused on the dysfunction of the glutamatergic and cholinergic neurotransmitter systems in Alzheimer’s disease (AD). However, there is now growing evidence in support of a GABAergic contribution to the pathogenesis of this neurodegenerative disease. Previous studies paint a complex, convoluted and often inconsistent picture of AD-associated GABAergic remodeling. Given the importance of the GABAergic system in neuronal function and homeostasis, in the maintenance of the excitatory/inhibitory balance, and in the processes of learning and memory, such changes in GABAergic function could be an important factor in both early and later stages of AD pathogenesis. Given the limited scope of currently available therapies in modifying the course of the disease, a better understanding of GABAergic remodeling in AD could open up innovative and novel therapeutic opportunities.
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Loss of GABA, the primary inhibitory neurotransmitter in the brain, is a key component of Alzheimer's disease.
“Loss of GABA, the primary inhibitory neurotransmitter in the brain, is a key component of AD.”
From Apolipoprotein E4, inhibitory network dysfunction, and Alzheimer’s disease (2019) · cites this paper as [84]
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Self-citationPathological mechanisms and therapeutic strategies for Alzheimer’s disease
Tam, K. Y., & Ju, Y. (2021) · Neural Regeneration Research · doi:10.4103/1673-5374.320970 · Cited by 416 · see citing works
Influence of glutamate and GABA transport on brain excitatory/inhibitory balance
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Alzheimer’s disease brain-derived extracellular vesicles spread tau pathology in interneurons
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GABAergic Inhibitory Interneuron Deficits in Alzheimer’s Disease: Implications for Treatment
Xu, Y., Zhao, M., Han, Y., & Zhang, H. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00660 · Cited by 203 · see citing works
Apolipoprotein E4, inhibitory network dysfunction, and Alzheimer’s disease
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Glutamate and GABA in Microglia-Neuron Cross-Talk in Alzheimer’s Disease
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Neural oscillations and brain stimulation in Alzheimer’s disease
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The GABAergic system as a therapeutic target for Alzheimer's disease
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Positive allosteric modulation of GABAA receptors by a novel antiepileptic drug cenobamate
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The Many Faces of Astrocytes in Alzheimer's Disease
Monterey, M. D., Wei, H., Wu, X., & Wu, J. Q. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2021.619626 · Cited by 117 · see citing works
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Unsupervised excitation: GABAergic dysfunctions in Alzheimer’s disease
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Self-citationThe GABAergic system in Alzheimer’s disease: a systematic review with meta-analysis
Carello-Collar, G., Bellaver, B., Ferreira, P. C. L., Ferrari-Souza, J. P., Ramos, V. G., Therriault, J., Tissot, C., De Bastiani, M. A., Soares, C., Pascoal, T. A., et al. (2023) · Molecular Psychiatry · doi:10.1038/s41380-023-02140-w · Cited by 98 · see citing works
Learning interpretable cellular and gene signature embeddings from single-cell transcriptomic data
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Sex- and age-related changes in GABA signaling components in the human cortex
Pandya, M., Palpagama, T. H., Turner, C. P., Waldvogel, H. J., Faull, R. L. M., & Kwakowsky, A. (2019) · Biology of Sex Differences · doi:10.1186/s13293-018-0214-6 · Cited by 88 · see citing works
Self-citationImpaired Expression of GABA Signaling Components in the Alzheimer’s Disease Middle Temporal Gyrus
Govindpani, K., Turner, C. P., Waldvogel, H. J., Faull, R. L. M., & Kwakowsky, A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21228704 · Cited by 82 · see citing works
Self-citationβ-Carboline as a Privileged Scaffold for Multitarget Strategies in Alzheimer’s Disease Therapy
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Therapeutic potential of quinazoline derivatives for Alzheimer's disease: A comprehensive review
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The Effect of Oral GABA on the Nervous System: Potential for Therapeutic Intervention
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Self-citationThe Role of the Microbiota–Gut–Brain Axis and Antibiotics in ALS and Neurodegenerative Diseases
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Glia: A major player in glutamate–GABA dysregulation‐mediated neurodegeneration
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Regulation of Melatonin and Neurotransmission in Alzheimer’s Disease
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Role of Receptors in Relation to Plaques and Tangles in Alzheimer’s Disease Pathology
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Synaptosome microRNAs regulate synapse functions in Alzheimer’s disease
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Self-citationAromas Influencing the GABAergic System
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Current Progress on Central Cholinergic Receptors as Therapeutic Targets for Alzheimer's Disease
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Hydrogel Film-Immobilized Lactobacillus brevis RK03 for γ-Aminobutyric Acid Production
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Dementia-related psychosis and the potential role for pimavanserin
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Current and Emerging Pharmacological Targets for the Treatment of Alzheimer’s Disease
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The hippocampus associated GABAergic neural network impairment in early-stage of Alzheimer's disease
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GABA A Receptors Are Well Preserved in the Hippocampus of Aged Mice
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Family C G-Protein-Coupled Receptors in Alzheimer’s Disease and Therapeutic Implications
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GABA levels decline with age: A longitudinal study
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Basal forebrain metabolism in Alzheimer's disease continuum: relationship with education
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Subject-specific features of excitation/inhibition profiles in neurodegenerative diseases
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Alterations of GABA B receptors in the APP/PS1 mouse model of Alzheimer's disease
Salazar, A., Osse, A. M. L., Ortiz, A. A., Murtishaw, A. S., & Kinney, J. W. (2020) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2020.10.013 · Cited by 24 · see citing works
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Sex differences of brain and their implications for personalized therapy
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Targeting GABAAR-Associated Proteins: New Modulators, Labels and Concepts
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Prefrontal GABA Levels Correlate with Memory in Older Adults at High Risk for Alzheimer’s Disease
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Alzheimer’s disease is an inherent, natural part of human brain aging: an integrated perspective
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CSF metabolites associated with biomarkers of Alzheimer’s disease pathology
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Neurotransmitter imbalance dysregulates brain dynamic fluidity in frontotemporal degeneration
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Beta-Amyloid (Aβ1-42) Increases the Expression of NKCC1 in the Mouse Hippocampus
Lam, P., Vinnakota, C., Guzmán, B. C., Newland, J., Peppercorn, K., Tate, W. P., Waldvogel, H. J., Faull, R. L. M., & Kwakowsky, A. (2022) · Molecules · doi:10.3390/molecules27082440 · Cited by 17 · see citing works
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Soluble β-amyloid impaired the GABA inhibition by mediating KCC2 in early APP/PS1 mice
Zhou, Y., Cheng, Y., Li, Y., Ma, J., Wu, Z., Chen, Y., Mei, J., & Chen, M. (2021) · BioScience Trends · doi:10.5582/bst.2021.01245 · Cited by 17 · see citing works
Therapeutic potential of alpha 5 subunit containing GABA A receptors in Alzheimer’s disease
Kwakowsky, A., Waldvogel, H. J., & Faull, R. L. M. (2021) · Neural Regeneration Research · doi:10.4103/1673-5374.300987 · Cited by 15 · see citing works
Self-citationTDP-43 regulates GAD1 mRNA splicing and GABA signaling in Drosophila CNS
Romano, G., Holodkov, N., Klima, R., & Feiguin, F. M. (2021) · Scientific Reports · doi:10.1038/s41598-021-98241-z · Cited by 15 · see citing works
Modifiable risk factors of dementia linked to excitation-inhibition imbalance
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Transcriptomic analysis reveals sex-specific patterns in the hippocampus in Alzheimer’s disease
Onisiforou, A., Christodoulou, C. C., Zamba‐Papanicolaou, E., Zanos, P., & Georgiou, P. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1345498 · Cited by 14 · see citing works
Spagnuolo, M. S., Mazzoli, A., Nazzaro, M., Troise, A. D., Gatto, C., Tonini, C., Colardo, M., Segatto, M., Scaloni, A., Pallottini, V., et al. (2022) · Molecular Neurobiology · doi:10.1007/s12035-022-03115-8 · Cited by 14 · see citing works
Parvalbumin as a sex-specific target in Alzheimer’s disease research – A mini-review
Terstege, D. J., & Epp, J. R. (2023) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2023.105370 · Cited by 14 · see citing works
Carton, L., Auger, F., Kyheng, M., Pétrault, M., Durieux, N., Allorge, D., Cottencin, O., Jardri, R., Bordet, R., & Rolland, B. (2019) · Scientific Reports · doi:10.1038/s41598-019-47187-4 · Cited by 14 · see citing works
Baseline Prediction of rTMS efficacy in Alzheimer patients
Lithgow, B., Dastgheib, Z. A., & Moussavi, Z. (2021) · Psychiatry Research · doi:10.1016/j.psychres.2021.114348 · Cited by 14 · see citing works
- Authors
- Govindpani, K., Calvo-Flores Guzmán, B., Vinnakota, C., Waldvogel, H., Faull, R., & Kwakowsky, A.
- Affiliations
- University of Auckland (NZ)
- Centre for Brain Research, Department of Anatomy and Medical Imaging, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1023, New Zealand
- Corresponding author
- Kwakowsky, Andrea
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2017-08-21
- Volume
- 18
- Issue
- 8
- Pages
- 1813
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC5578199
- OpenAlex
- W2746415584
- Cited by
- 208
- References
- 353
- Citations by year
- 2026: 20 · 2025: 14 · 2024: 25 · 2023: 26 · 2022: 16 · 2021: 41 · 2020: 29 · 2019: 29 · 2018: 5 · 2017: 2 · 2012: 1
- FWCI
- 2.18
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- ResearchSpace (University of Auckland) (submittedVersion, cc-by)
- Funders
- Aotearoa Foundation (3705579)
- Brain Research New Zealand (3710638)
- Health Research Council of New Zealand (3627373)
- Maurice and Phyllis Paykel Trust (3713650)
- Auckland Medical Research Foundation (3712563)
- University of Otago (110089.01)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, GABAergic system, inhibitory neurotransmission, excitation-inhibition balance, neurodegeneration, AD pathogenesis, therapeutic target
- MeSH terms
- Alzheimer Disease, Brain, gamma-Aminobutyric Acid, Humans, Neurotransmitter Agents, GABAergic Neurons
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