Cited by 159Alzheimer's disease research and treatmentsNeuroscience and Neuropharmacology ResearchNeuroinflammation and Neurodegeneration Mechanisms

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Biochemical and molecular studies of NMDA receptor subunits NR1/2A/2B in hippocampal subregions throughout progression of Alzheimer's disease pathology

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Mishizen-Eberz, Amanda J, Rissman, Robert A, Carter, Troy L, Ikonomovic, Milos D, Wolfe, Barry B, Armstrong, David M·2004·Neurobiology of Disease

DOI 10.1016/j.nbd.2003.09.016

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Abstract

Alzheimer's disease (AD) is characterized by loss of specific cell populations within selective subregions of the hippocampus. Excitotoxicity, mediated via ionotropic glutamate receptors, may play a crucial role in this selective neuronal vulnerability. We investigated whether alterations in NMDA receptor subunits occurred during AD progression. Employing biochemical and in situ hybridization techniques in subjects with a broad range of AD pathology, protein levels, and mRNA expression of NR1/2A/2B subunits were assayed. With increasing AD neuropathology, protein levels and mRNA expression for NR1/2B subunits were significantly reduced, while the NR2A subunit mRNA expression and protein levels were unchanged. Cellular analysis of neuronal mRNA expression revealed a significant increase in the NR2A subunit in subjects with moderate neurofibrillary tangle neuropathology. This investigation supports the hypothesis that alterations occur in the expression of specific NMDA receptor subunits with increasing AD pathologic severity, which is hypothesized to contribute to the vulnerability of these neurons.

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Authors: Mishizen-Eberz, A. J., Rissman, R. A., Carter, T. L., Ikonomovic, M. D., Wolfe, B. B., & Armstrong, D. M.
Affiliations: Lankenau Institute for Medical Research (US)
Georgetown University Medical Center (US)
Corresponding author: Mishizen-Eberz, Amanda J
ORCID: Rissman, Robert A
Venue: Neurobiology of Disease
Publisher: Elsevier BV
Published: 2004-02
Volume: 15
Issue: 1
Pages: 80-92
ISSN: 0969-9961 (ISSN-L)
DOI: 10.1016/j.nbd.2003.09.016
OpenAlex: W2024849224
Cited by: 156
References: 55
Citations by year: 2026: 4 · 2025: 5 · 2024: 7 · 2023: 4 · 2022: 9 · 2021: 7 · 2020: 5 · 2019: 5 · 2018: 6 · 2017: 7 · 2016: 10 · 2015: 8 · 2014: 12 · 2013: 7 · 2012: 6
FWCI: 1.53
Type: journal article
Language: en
Open access: green
doaj.org
Licence: cc-by-sa
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neurobiology of Disease (publishedVersion)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: National Institutes of Health (5r01ag008206-15)
National Institute on Aging (AG 08206)
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
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords: Alzheimer's disease, NMDA receptor subunits, NR1, NR2A, NR2B, hippocampus, excitotoxicity, ionotropic glutamate receptors, neurofibrillary tangles, selective neuronal vulnerability, mRNA expression, protein abundance, disease progression
MeSH terms: Aged, Aged, 80 and over, Alzheimer Disease, Female, Hippocampus, Humans, Immunohistochemistry, Male, Middle Aged, Neurons, RNA, Messenger, Down-Regulation, Up-Regulation, Receptors, N-Methyl-D-Aspartate, Neurofibrillary Tangles, Disease Progression, Protein Subunits

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Biochemical and molecular studies of NMDA receptor subunits NR1/2A/2B in hippocampal subregions throughout progression of Alzheimer's disease pathology

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