Unique Lipoproteins Secreted by Primary Astrocytes From Wild Type, apoE (−/−), and Human apoE Transgenic Mice
Open accessAbstract
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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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.”
From Neurotoxic reactive astrocytes induce cell death via saturated lipids (2021) · cites this paper as [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”
From Neurotoxic reactive astrocytes induce cell death via saturated lipids (2021) · cites this paper as [11]
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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.
- ORCID
- 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
- hybrid
- doi.org
- Licence
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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