Cited by 180Alzheimer's disease research and treatmentsCholesterol and Lipid MetabolismLipoproteins and Cardiovascular Health

Purification and characterization of astrocyte-secreted apolipoprotein E and J-containing lipoproteins from wild-type and human apoE transgenic mice

DeMattos, Ronald B, Brendza, Robert P, Heuser, John E, Kierson, Malca, Cirrito, John R, Fryer, John, Sullivan, Patrick M, Fagan, Anne M +2 more·2001·Neurochemistry International

Abstract

The varepsilon4 allele of apolipoprotein E (apoE) is a genetic risk factor for Alzheimer's disease (AD). In order to gain a better understanding of the molecular mechanisms by which apoE and possibly other apolipoproteins produced in the central nervous system (CNS) influence AD pathogenesis, we have purified and characterized the two most abundant apolipoproteins produced in the CNS, apoE and apoJ. We purified apoE and apoJ from primary cultures of mouse astrocytes, which were derived from transgenic mice expressing human apoE isoforms in the absence of mouse apoE. Utilizing antibody affinity columns, we were able to purify both human apoE3 and apoE4, as well as mouse apoJ-containing lipoproteins. Astrocyte-secreted human apoE was present in high density-like lipoproteins of three predominant sizes ranging from 8 to 15 nm in diameter. Mouse apoJ was in particles between 10 and 17 nm in diameter with a peak size range of approximately 11 nm. ApoE and apoJ were in distinct lipoproteins. Utilization of quick-freeze, deep-etch electron microscopy revealed the apoE particles were discs while the apoJ particles were smaller and more irregular in appearance. The lipid composition of apoE particles was very different from those containing apoJ. ApoE-particles contained a similar mass of apoE and lipid, with cholesterol and phospholipid being about equal in mass per particle. ApoJ-particles were relatively lipid poor (three parts protein, one part lipid), with phospholipids being much more abundant than cholesterol. Detailed characterization of phospholipid composition by electrospray ionization mass spectrometry analysis revealed ethanolamine glycerophospholipids to be the most abundant phospholipid present in both apoE and apoJ particles. Analysis of cerebrospinal fluid from apoE3 and apoE4 transgenic mice revealed that human and mouse apoE were in particles the same size as those secreted by astrocytes. Further use of physiological preparations of CNS-derived lipoproteins may allow for a detailed understanding of the role of these molecules in the normal brain and in diseases such as AD.

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Crossref · 10.1016/s0197-0186(01)00049-3

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  • Long-chain saturated FFAs and VLCPCs are normally of relatively low abundance in membranes and ApoE- and ApoJ-containing lipoparticles.

    “lipids that are normally of relatively low abundance in membranes and ApoE- and ApoJ-containing lipoparticles14”

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Authors
DeMattos, R. B., Brendza, R. P., Heuser, J. E., Kierson, M., Cirrito, J. R., Fryer, J., Sullivan, P. M., Fagan, A. M., Han, X., & Holtzman, D. M.
Affiliations
  • Washington University in St. Louis (US)
  • Duke University (US)
Corresponding author
Holtzman, David M
Venue
Neurochemistry International
Publisher
Elsevier BV
Published
2001-11
Volume
39
Issue
5-6
Pages
415-425
ISSN
0197-0186 (ISSN-L)
OpenAlex
W2017404389
Cited by
180
References
74
Citations by year
2026: 4 · 2025: 8 · 2024: 6 · 2023: 6 · 2022: 5 · 2021: 6 · 2020: 7 · 2019: 10 · 2018: 7 · 2017: 6 · 2016: 13 · 2015: 6 · 2014: 10 · 2013: 6 · 2012: 8
FWCI
5.19
Type
journal article
Language
en
Open access
closed
Locations
  • Neurochemistry International (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • James S. McDonnell Foundation
  • National Institutes of Health
  • National Institute on Aging (AG00861, AG 05681, P50AG005681, AG13956)
  • National Institute of General Medical Sciences (GM29647, R01GM029647)
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, clusterin, astrocytes, lipoprotein secretion, APOE ε4, APOE3, Alzheimer's disease, high-density lipoprotein, lipoprotein particle size, phospholipid composition, ethanolamine glycerophospholipids, cerebrospinal fluid
MeSH terms
Animals, Apolipoproteins E, Astrocytes, Cells, Cultured, Glycoproteins, Humans, Lipids, Lipoproteins, Lipoproteins, HDL, Mice, Transgenic, Particle Size, Phospholipids, Reference Values, Molecular Chaperones, Clusterin, Mice

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