The DOI matches its Crossref record; 73 of the 73 references it cites were found in a registry or an index.
Deficient glutamate tranport is associated with neurodegeneration in Alzheimer's disease
Abstract
The mechanisms of synapse damage in Alzheimer's disease (AD) are not fully understood. Deficient functioning of glutamate transporters might be involved in synaptic pathology and neurodegeneration by failing to clear excess glutamate at the synaptic cleft. In AD, glutamate transporter activity as assessed by D-[3H]aspartate binding is decreased; however, it is not clear to what extent it is associated with the neurodegenerative process and cognitive alterations. For this purpose, levels of D- and L-[3H]aspartate binding in midfrontal cortex were correlated with synaptophysin levels, brain spectrin degradation product levels, and clinical and neuropathological indicators of AD. Compared to control brains, AD brains displayed a 34% decrease in levels of D-[3H]aspartate binding, a 30% decrease in L-[3H]aspartate binding, and a 48% loss of synaptophysin immunoreactivity. Increased levels of brain spectrin degradation products correlated with a decrease in levels of D-[3H] and L-[3H]aspartate binding, and decreased levels of synaptophysin immunoreactivity. Levels of L-[3H]aspartate binding correlated with levels of synaptophysin immunoreactivity. These results suggest that decreased glutamate transporter activity in AD is associated with increased excitotoxicity and neurodegeneration, supporting the possibility that abnormal functioning of this system might be involved in the pathogenesis of synaptic damage in AD.
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In the citing paper
“Glutamine is produced from glutamate by the activity of glutamine synthetase (GS) [124,131].”
From Mitochondrial Oxidative and Nitrosative Stress and Alzheimer Disease (2020) · cites this paper as [131]
In the citing paper
“but its activity is decreased in AD brain, which is likely due to oxidative modification by HNE [26,131].”
From Mitochondrial Oxidative and Nitrosative Stress and Alzheimer Disease (2020) · cites this paper as [131]
In the citing paper
“The glial glutamate transporter (GLT-1), also known as the excitatory amino acid transporter-2 (EAAT2), is responsible for the uptake of synaptic glutamate”
From Mitochondrial Oxidative and Nitrosative Stress and Alzheimer Disease (2020) · cites this paper as [131]
In the citing paper
“Loss or dysfunction of SLC1A2 has been implicated in multiple neurodegenerative and neuropsychiatric disorders, including AD where it is closely associated with cognitive decline [126–131].”
From Tau Ablation Rewires Brain Cell Programs in Health and Restores Function in Disease (2026) · cites this paper as [129]
In the citing paper
“EAAT2 expression diminishes with age60 and correlates with signs of neuronal death in postmortem brains of sporadic AD patients61.”
From The R136S mutation in the APOE3 gene confers resilience against tau pathology via inhibition of the cGAS-STING-IFN pathway (2025) · cites this paper as [61]
In the citing paper
“in postmortem brains of patients with sporadic AD correlates with signs of neuronal death56”
From APOE3 - R136S mutation confers resilience against tau pathology via cGAS-STING-IFN inhibition (2024) · cites this paper as [56]
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Cited by
Sorted by citations
Danbolt, N. C. (2001) · Progress in Neurobiology · doi:10.1016/s0301-0082(00)00067-8 · Cited by 4,227
Role of Glutamate and NMDA Receptors in Alzheimer’s Disease
Wang, R., & Reddy, P. H. (2017) · Journal of Alzheimer’s Disease · doi:10.3233/jad-160763 · Cited by 1,009
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Metadata
- Authors
- Masliah, E., Hansen, L., Alford, M., Deteresa, R., & Mallory, M.
- Affiliations
- University of California San Diego (US)
- Corresponding author
- Masliah, E.
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 1996-11
- Volume
- 40
- Issue
- 5
- Pages
- 759-766
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- OpenAlex
- W2050523782
- Cited by
- 476
- References
- 73
- Citations by year
- 2026: 13 · 2025: 17 · 2024: 20 · 2023: 17 · 2022: 27 · 2021: 21 · 2020: 24 · 2019: 32 · 2018: 24 · 2017: 17 · 2016: 11 · 2015: 20 · 2014: 13 · 2013: 10 · 2012: 12
- FWCI
- 6.74
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG10689, AG05131, R01AG010689, P50AG005131)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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, glutamate transporters, excitotoxicity, neurodegeneration, synapse damage, synaptophysin, synaptic pathology
- MeSH terms
- Aged, Aspartic Acid, Autopsy, Biological Transport, Brain, Frontal Lobe, Humans, Nerve Degeneration, Organ Specificity, Reference Values, Regression Analysis, Spectrin, Biomarkers, Synaptophysin, Neurofibrillary Tangles, ATP-Binding Cassette Transporters, Amino Acid Transport System X-AG
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