Cited by 213Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsBarrier Structure and Function Studies

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Glial fibrillary acidic protein-apolipoprotein E (apoE) transgenic mice: astrocyte-specific expression and differing biological effects of astrocyte-secreted apoE3 and apoE4 lipoproteins.

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Sun, Yuling, Wu, Shan, Bu, Guojun, Onifade, Moyosore K., Patel, Shilen N., LaDu, Mary Jo, Fagan, Anne M., Holtzman, David M.·1998·The Journal of Neuroscience

DOI 10.1523/jneurosci.18-09-03261.1998PMC PMC6792658

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Abstract

The ε4 allele of apolipoprotein E (apoE) is associated with increased risk for Alzheimer’s disease (AD) and poor outcome after brain injury. In the CNS, apoE is expressed by glia, predominantly astrocytes. To define the potential biological functions of different human apoE isoforms produced within the brain, transgenic mice were generated in which human apoE3 and apoE4 expression is under control of the astrocyte-specific glial fibrillary acidic protein (GFAP) promoter. These animals were then bred back to apoE knock-out mice. Human apoE protein is found within astrocytes and the neuropil throughout development and into the adult period, as assessed by immunocytochemistry and immunoblot analysis in several GFAP-apoE3 and E4 lines. Cultured astrocytes from these mice secrete apoE3 and apoE4 in lipoproteins that are high-density lipoprotein-like in size. When primary hippocampal neurons are grown in the presence of astrocyte monolayers derived from these transgenic mice, there is significantly greater neurite outgrowth from neurons grown in the presence of apoE3-secreting astrocytes compared with apoE4-secreting or apoE knock-out astrocytes. These effects are not dependent on direct astrocyte–neuron contact and appear to require the low-density lipoprotein receptor-related protein. These data suggest that astrocyte-secreted, apoE3-containing lipoproteins have different biological effects than apoE4-containing lipoproteins. In addition to providing information regarding the role of astrocyte-secreted apoE lipoproteins in the normal brain, these animals will also be useful in models of both AD and CNS injury.

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Self-citation
Glial Fibrillary Acidic Protein: GFAP-Thirty-One Years (1969–2000)
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Self-citation

See all 213

Authors: Sun, Y., Wu, S., Bu, G., Onifade, M. K., Patel, S. N., LaDu, M. J., Fagan, A. M., & Holtzman, D. M.
Affiliations: Washington University in St. Louis (US)
University of Chicago (US)
ORCID: Sun, Yuling
Wu, Shan
Bu, Guojun
LaDu, Mary Jo
Fagan, Anne M.
Holtzman, David M.
Venue: The Journal of Neuroscience
Publisher: Society for Neuroscience
Published: 1998-05-01
Volume: 18
Issue: 9
Pages: 3261-3272
ISSN: 0270-6474 (ISSN-L)
1529-2401
DOI: 10.1523/jneurosci.18-09-03261.1998
PMC: PMC6792658
OpenAlex: W1629602451
Cited by: 213
References: 81
Citations by year: 2026: 1 · 2025: 3 · 2024: 3 · 2023: 1 · 2022: 6 · 2021: 6 · 2020: 5 · 2019: 4 · 2018: 4 · 2017: 7 · 2016: 2 · 2015: 2 · 2014: 7 · 2013: 1 · 2012: 1
FWCI: 12.91
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-sa
creativecommons.org/licenses/by-nc-sa/4.0/ (vor, 184 d)
Locations: Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
Funders: Alzheimer's Association (AG05681, AG13956)
National Institutes of Health (AG05681, AG13956)
National Institute on Aging (R01AG013956, AG 05681, P50AG005681, R37AG013956, AG13956)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Keywords: apolipoprotein E, APOE3, APOE ε4, astrocytes, glial fibrillary acidic protein, neurite outgrowth, hippocampal neurons, low density lipoprotein receptor-related protein, Alzheimer's disease, central nervous system injury, astrocyte-neuron interaction
MeSH terms: Animals, Apolipoproteins E, Astrocytes, Brain, Cells, Cultured, Gene Expression Regulation, Glial Fibrillary Acidic Protein, Humans, Mice, Transgenic, Particle Size, Mice, Apolipoprotein E3, Apolipoprotein E4

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Glial fibrillary acidic protein-apolipoprotein E (apoE) transgenic mice: astrocyte-specific expression and differing biological effects of astrocyte-secreted apoE3 and apoE4 lipoproteins.

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