Glutamate Transporter Alterations in Alzheimer Disease Are Possibly Associated with Abnormal APP Expression
Abstract
Recent studies have shown that deficient functioning of glutamate transporters (GTs) in Alzheimer disease (AD) might lead to neurodegeneration. The main objectives of the present study were to determine which GT subtype is most affected in AD and to asses to what extent altered GT function is associated with abnormal amyloid precursor protein (APP) expression. While EAAT2-immunoreactivity (IR) was decreased in AD frontal cortex, EAAT1- and EAAT3-IR were unaffected; mRNA levels for all 3 GTs were not affected. Decreased EAAT2-IR was associated with decreased GT activity. EAAT2-IR inversely correlated with EAAT2 mRNA levels, suggesting that in AD, GT expression alterations occur due to disturbance at the post-transcriptional level. EAAT2-IR was inversely correlated with APP770 mRNA. In addition, GT activity directly correlated with APP695 mRNA and total APP protein levels, and inversely correlated with APP751/770 mRNA levels. This study supports the notion that astroglial EAAT2 is affected in AD and abnormal functioning and/or processing of APP might play an important role in this process.
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GLT-1 shows dysfunction or decreased expression in patients with neurodegenerative diseases such as PD, AD, or ALS.
“GLT-1 shows dysfunction or decreased expression in patients with neurodegenerative diseases such as PD [26], AD [27], or ALS [17]”
From Neuroprotective Effect of Ceftriaxone on MPTP‐Induced Parkinson’s Disease Mouse Model by Regulating Inflammation and Intestinal Microbiota (2021) · cites this paper as [27]
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- Authors
- LI, S., MALLORY, M., ALFORD, M., TANAKA, S., & MASLIAH, E.
- Affiliations
- University of California San Diego (US)
- Corresponding author
- MASLIAH, ELIEZER
- Venue
- Journal of Neuropathology and Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 1997-08
- Volume
- 56
- Issue
- 8
- Pages
- 901-911
- ISSN
- 0022-3069 (ISSN-L)
- OpenAlex
- W2075770826
- Cited by
- 343
- References
- 0
- Citations by year
- 2026: 4 · 2025: 12 · 2024: 13 · 2023: 6 · 2022: 15 · 2021: 16 · 2020: 17 · 2019: 10 · 2018: 13 · 2017: 14 · 2016: 9 · 2015: 18 · 2014: 8 · 2013: 12 · 2012: 16
- FWCI
- 4.49
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuropathology & Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG10689, AG05131, R01AG010689, P50AG005131)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- Alzheimer's disease, glutamate transporters, GLT-1, GLAST, EAAT3, amyloid precursor protein, APP processing, astrocytes, post-transcriptional regulation, frontal cortex, neurodegeneration
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Brain, Cerebral Cortex, Frontal Lobe, Humans, Molecular Sequence Data, RNA, Messenger, Tissue Distribution, Blotting, Western, Amyloid beta-Protein Precursor, ATP-Binding Cassette Transporters, Amino Acid Transport System X-AG
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