Cited by 177Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

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Gene expression correlates of neurofibrillary tangles in Alzheimer's disease

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Dunckley, Travis, Beach, Thomas G., Ramsey, Keri E., Grover, Andrew, Mastroeni, Diego, Walker, Douglas G., LaFleur, Bonnie J., Coon, Keith D., Brown, Kevin M., Caselli, Richard, Kukull, Walter, Higdon, Roger, McKeel, Daniel, Morris, John C., Hulette, Christine, Schmechel, Donald, Reiman, Eric M., Rogers, Joseph, Stephan, Dietrich A.·2006·Neurobiology of Aging

DOI 10.1016/j.neurobiolaging.2005.08.013PMC PMC2259291

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Abstract

Neurofibrillary tangles (NFT) constitute one of the cardinal histopathological features of Alzheimer's disease (AD). To explore in vivo molecular processes involved in the development of NFTs, we compared gene expression profiles of NFT-bearing entorhinal cortex neurons from 19 AD patients, adjacent non-NFT-bearing entorhinal cortex neurons from the same patients, and non-NFT-bearing entorhinal cortex neurons from 14 non-demented, histopathologically normal controls (ND). Of the differentially expressed genes, 225 showed progressively increased expression (AD NFT neurons > AD non-NFT neurons > ND non-NFT neurons) or progressively decreased expression (AD NFT neurons < AD non-NFT neurons < ND non-NFT neurons), raising the possibility that they may be related to the early stages of NFT formation. Immunohistochemical studies confirmed that many of the implicated proteins are dysregulated and preferentially localized to NFTs, including apolipoprotein J, interleukin-1 receptor-associated kinase 1, tissue inhibitor of metalloproteinase 3, and casein kinase 2, beta. Functional validation studies are underway to determine which candidate genes may be causally related to NFT neuropathology, thus providing therapeutic targets for the treatment of AD.

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Authors: Dunckley, T., Beach, T. G., Ramsey, K. E., Grover, A., Mastroeni, D., Walker, D. G., LaFleur, B. J., Coon, K. D., Brown, K. M., Caselli, R., Kukull, W., Higdon, R., McKeel, D., Morris, J. C., Hulette, C., Schmechel, D., Reiman, E. M., Rogers, J., & Stephan, D. A.
Affiliations: Translational Genomics Research Institute (US)
Vanderbilt University (US)
Mayo Clinic (US)
National Alzheimer's Coordinating Center (US)
Duke University (US)
Corresponding author: Stephan, Dietrich A.
ORCID: Dunckley, Travis
Beach, Thomas G.
Ramsey, Keri E.
Mastroeni, Diego
Walker, Douglas G.
LaFleur, Bonnie J.
Caselli, Richard
Kukull, Walter
Morris, John C.
Reiman, Eric M.
Stephan, Dietrich A.
Venue: Neurobiology of Aging
Publisher: Elsevier BV
Published: 2006-10
Volume: 27
Issue: 10
Pages: 1359-1371
ISSN: 0197-4580 (ISSN-L)
DOI: 10.1016/j.neurobiolaging.2005.08.013
PMC: PMC2259291
OpenAlex: W2005889734
Cited by: 177
References: 35
Citations by year: 2026: 2 · 2025: 8 · 2024: 8 · 2023: 14 · 2022: 11 · 2021: 10 · 2020: 15 · 2019: 10 · 2018: 10 · 2017: 5 · 2016: 9 · 2015: 12 · 2014: 10 · 2013: 9 · 2012: 9
FWCI: 3.60
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neurobiology of Aging (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health (1k01ag024079-01a2)
National Institute on Aging (P30-AG-19610, AG05 128, R01AG023193, 1-RO1-AG023193, U01AG016976, K01-AG-024079, P50AG005128, P 50 AG05681, P50AG005681, P30AG019610, P01 AG0 3991, P01AG003991)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords: neurofibrillary tangles, Alzheimer's disease, gene expression profiling, differentially expressed genes, clusterin, TIMP-3, casein kinase 2, therapeutic target
MeSH terms: Aged, 80 and over, Female, Humans, Male, Nerve Tissue Proteins, Gene Expression, Neurofibrillary Tangles, Entorhinal Cortex, Gene Expression Profiling

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Gene expression correlates of neurofibrillary tangles in Alzheimer's disease

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