Cited by 222Alzheimer's disease research and treatmentsCholesterol and Lipid MetabolismLipoproteins and Cardiovascular Health

Unique Lipoproteins Secreted by Primary Astrocytes From Wild Type, apoE (−/−), and Human apoE Transgenic Mice

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Fagan, Anne M., Holtzman, David M., Munson, Gregory, Mathur, Tanya, Schneider, Danielle, Chang, Louis K., Getz, Godfrey S., Reardon, Catherine A. +3 more·1999·Journal of Biological Chemistry

Abstract

Composition of central nervous system lipoproteins affects the metabolism of lipoprotein constituents within the brain. The epsilon4 allele of apolipoprotein E (apoE) is a risk factor for Alzheimer's disease via an unknown mechanism(s). As glia are the primary central nervous system cell type that synthesize apoE, we characterized lipoproteins secreted by astrocytes from wild type (WT), apoE (-/-), and apoE transgenic mice expressing human apoE3 or apoE4 in a mouse apoE (-/-) background. Nondenaturing size exclusion chromatography demonstrates that WT, apoE3, and apoE4 astrocytes secrete particles the size of plasma high density lipoprotein (HDL) composed of phospholipid, free cholesterol, and protein, primarily apoE and apoJ. However, the lipid:apoE ratio of particles containing human apoE is significantly lower than WT. ApoE localizes across HDL-like particle sizes. ApoJ localizes to the smallest HDL-like particles. ApoE (-/-) astrocytes secrete little phospholipid or free cholesterol despite comparable apoJ expression, suggesting that apoE is required for normal secretion of astrocyte lipoproteins. Further, particles were not detected in apoE (-/-) samples by electron microscopy. Nondenaturing immunoprecipitation experiments indicate that apoE and apoJ reside predominantly on distinct particles. These studies suggest that apoE expression influences the unique structure of astrocyte lipoproteins, a process further modified by apoE species.

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Crossref · 10.1074/jbc.274.42.30001

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  • ApoE and ApoJ are found in HDL-like fractions, with an increase in ApoJ concentration within HDL-like fractions.

    “we found ApoE and ApoJ in HDL-like fractions, with an increase in ApoJ concentration within HDL-like fractions (Extended Data Figure 4)11.”
  • ApoE and ApoJ are predominantly secreted in lipidated lipoparticles.

    “Consistent with the hypothesis that ApoE and ApoJ are predominantly secreted in lipidated lipoparticles, we found ApoE and ApoJ in HDL-like fractions”

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Research works printed but not linked: 10

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Authors
Fagan, A. M., Holtzman, D. M., Munson, G., Mathur, T., Schneider, D., Chang, L. K., Getz, G. S., Reardon, C. A., Lukens, J., Shah, J. A., & LaDu, M. J.
Affiliations
  • Washington University in St. Louis (US)
  • University of Chicago (US)
Corresponding author
Fagan, Anne M.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
1999-10
Volume
274
Issue
42
Pages
30001-30007
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2163481458
Cited by
222
References
70
Citations by year
2026: 4 · 2025: 7 · 2024: 11 · 2023: 5 · 2022: 12 · 2021: 5 · 2020: 12 · 2019: 7 · 2018: 3 · 2017: 6 · 2016: 11 · 2015: 12 · 2014: 11 · 2013: 4 · 2012: 5
FWCI
3.60
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Alzheimer's Association (AG05681, AG13956)
  • American Health Assistance Foundation
  • University of Missouri
  • National Institutes of Health (AG05681, AG13956)
  • National Institute on Aging (R01AG013956, AG00861-01, AG05681-16, P50AG005681, AG13956)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
Keywords
apolipoprotein E, astrocytes, lipoprotein secretion, clusterin, APOE ε4, APOE3, ApoE-deficient mice, Alzheimer's disease risk, free cholesterol, phospholipids
MeSH terms
Animals, Apolipoproteins E, Astrocytes, Cells, Cultured, Chromatography, Gel, Electrophoresis, Polyacrylamide Gel, Humans, Lipoproteins, Mice, Transgenic, Microscopy, Electron, Mice

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