Cited by 199Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsNeuroscience and Neuropharmacology Research

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GABAergic Function in Alzheimer's Disease: Evidence for Dysfunction and Potential as a Therapeutic Target for the Treatment of Behavioural and Psychological Symptoms of Dementia

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Lanctôt, Krista L, Herrmann, Nathan, Mazzotta, Paolo, Khan, Lyla R, Ingber, Neil·2004·The Canadian Journal of Psychiatry

DOI 10.1177/070674370404900705

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Abstract

Alzheimer's disease (AD) is characterized by disruptions in multiple major neurotransmitters. While many studies have attempted to establish whether GABA is disrupted in AD patients, findings have varied. We review evidence for disruptions in GABA among patients with AD and suggest that the variable findings reflect subtypes of the disease that are possibly manifested clinically by differing behavioural symptoms. GABA, the major inhibitory neurotransmitter, has long been a target for anxiolytics, hypnotic sedatives, and anticonvulsants. We review the clinical use of GABAergic agents in treating persons with AD symptoms. While newer generation GABAergic medications are now available, they have yet to be evaluated among patients with AD.

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Monoamine Oxidase Inhibitors and Neuroprotection
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“It is also interesting to note that glutamate-associated excitotoxicity is also thought to play a role in the neurodegeneration observed in AD and GABAergic deficits have been reported in AD, although these latter findings are conflicting and complicated by variables such as illness severity and postmortem handling of…”
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Can zebrafish be used as animal model to study Alzheimer's disease?
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The role of synaptic activity in the regulation of amyloid beta levels in Alzheimer's disease
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The Brilliance of the Zebrafish Model: Perception on Behavior and Alzheimer’s Disease
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An immunohistochemical study of GABAA receptor gamma subunits in Alzheimer's disease hippocampus: Relationship to neurofibrillary tangle progression
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“psychological and behavioral symptoms in AD patients remains unclear as there have been few controlled clinical trials to date, which have yielded mixed results.(27) In addition, no study has focused on changes in benzodiazepine sensitivity in AD patients.”
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Use of Gabapentin in the Treatment of Behavioural and Psychological Symptoms of Dementia
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Alternative approaches for PET radiotracer development in Alzheimer's disease: imaging beyond plaque
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Altered neurochemical profile in the M cGill‐ R ‐ T hy1‐ APP rat model of A lzheimer's disease: a longitudinal in vivo 1 H MRS study
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“%) reductions in the GABA concentrations and GAD activity (Lanctôt et al., 2004).”
BackgroundInfluential
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Decreased GABA levels of the anterior and posterior cingulate cortex are associated with executive dysfunction in mild cognitive impairment
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“, 2019) and AD patients (Lanctôt et al., 2004; Bai et al., 2015), although the affected brain regions were different.”
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Brain type carnosinase in dementia: a pilot study
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“Post-mortem and imaging studies of AD have shown decreases in GABA in the temporal, frontal, and parietal regions [19].”
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Psychiatric and behavioral symptoms in Alzheimer’s disease and other dementias: Etiology and management
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“Biological theories have focused on the role of various neurotransmitter systems, including serotonin [5-HT] (aggression, depression, anxiety, psychosis) [7], dopamine [DA] (aggression, psychosis) [8], norepinephrine [NA] (aggression) [9], acetylcholine [ACh] (psychosis, apathy) [10] and γ-aminobutyric acid [GABA] [11…”
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Drug Development in Alzheimer’s Disease: The Contribution of PET and SPECT
Declercq, L., Vandenberghe, R. R., Laere, K. V., Verbruggen, A., & Bormans, G. M. (2016) · Frontiers in Pharmacology · doi:10.3389/fphar.2016.00088 · Cited by 27
“A more detailed discussion of the GABAsystem and its putative role in AD can be found in some extensive reviews (Marczynski, 1998; Lanctot et al., 2004; Rissman et al., 2007).”
Background
The role of monoamines in the development of Alzheimer's disease and neuroprotective effect of a proline rich polypeptide
Yenkoyan, K. B., Fereshetyan, K., Matinyan, S., Chavushyan, V. A., & Aghajanov, M. I. (2018) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2018.05.013 · Cited by 25
Role of Flavonoids in Mitigating the Pathological Complexities and Treatment Hurdles in Alzheimer's Disease
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“Furthermore, GABA and glutamic acid (Glu) are as major inhibitory and excitatory neurotransmitters respectively and are uniformly distributed in CNS. Decreased level of transition from Glutamate to GABA leads to high excitation and poor inhibition (Lanctôt et al. 2004).”
Synthesis of 4-substituted nipecotic acid derivatives and their evaluation as potential GABA uptake inhibitors
Hellenbrand, T., Höfner, G. C., Wein, T., & Wanner, K. T. (2016) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2016.03.038 · Cited by 24
An Overlooked Prebiotic: Beneficial Effect of Dietary Nucleotide Supplementation on Gut Microbiota and Metabolites in Senescence-Accelerated Mouse Prone-8 Mice
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Transgenic autoinhibition of p21-activated kinase exacerbates synaptic impairments and fronto-dependent behavioral deficits in an animal model of Alzheimer’s disease
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“The downregulation of key proteins related to the GABAergic system in the frontal, temporal and parietal cortices of AD patients is consistent with the view that GABAergic function plays a role in AD [79, 80].”
Result
Synthesis of 3‐Azabicyclo[3.2.0]heptane Derivatives as γ‐Aminobutyric Acid Analogues through Intermolecular [2+2] Photocycloaddition
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New insights into clinical trial for colostrinin™ in Alzheimer's disease
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“Importantly, GABA has been shown to be potential therapeutic target for controlling AD symptoms (30).”
In Vivo Imaging of Neurotransmission and Brain Receptors in Dementia
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Raman Spectrometric Detection Methods for Early and Non-Invasive Diagnosis of Alzheimer’s Disease
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“- aminobutyric acid (GABA), has been implicated in AD progression [65].”
The GABA–Working Memory Relationship in Alzheimer’s Disease
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“Initial postmortem studies report reduced GABA levels in the frontal, parietal and temporal cortices as compared to healthy age-matched controls [15].”
Creatine Enhances Transdifferentiation of Bone Marrow Stromal Cell-Derived Neural Stem Cell Into GABAergic Neuron-Like Cells Characterized With Differential Gene Expression
Darabi, S., Tiraihi, T., Delshad, A. A., Sadeghizadeh, M., Taheri, T., & Hassoun, H. K. (2016) · Molecular Neurobiology · doi:10.1007/s12035-016-9782-9 · Cited by 22

Authors: Lanctôt, K. L., Herrmann, N., Mazzotta, P., Khan, L. R., & Ingber, N.
Affiliations: Sunnybrook Health Science Centre (CA)
Corresponding author: Lanctôt, Krista L
ORCID: Lanctôt, Krista L
Herrmann, Nathan
Venue: The Canadian Journal of Psychiatry
Publisher: SAGE Publications
Published: 2004-07
Volume: 49
Issue: 7
Pages: 439-453
ISSN: 0706-7437 (ISSN-L)
1497-0015
DOI: 10.1177/070674370404900705
OpenAlex: W2184602814
Cited by: 191
References: 146
Citations by year: 2025: 7 · 2024: 6 · 2023: 6 · 2022: 11 · 2021: 14 · 2020: 12 · 2019: 13 · 2018: 19 · 2017: 15 · 2016: 11 · 2015: 9 · 2014: 8 · 2013: 9 · 2012: 6
FWCI: 3.09
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
Locations: The Canadian Journal of Psychiatry (publishedVersion)
PubMed (publishedVersion)
Funders: Alzheimer's Society
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: Alzheimer's disease, GABA, GABAergic dysfunction, behavioral and psychological symptoms of dementia, inhibitory neurotransmitter, GABAergic drugs, anxiolytics, antiepileptic drugs, disease subtypes
MeSH terms: Aged, Alzheimer Disease, Benzodiazepines, Binding Sites, Brain, Frontal Lobe, gamma-Aminobutyric Acid, Humans, Limbic System, Parietal Lobe, Temporal Lobe, Tomography, Emission-Computed, Tomography, Emission-Computed, Single-Photon, Receptors, GABA, GABA Agonists

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GABAergic Function in Alzheimer's Disease: Evidence for Dysfunction and Potential as a Therapeutic Target for the Treatment of Behavioural and Psychological Symptoms of Dementia

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