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Cited by 383Lipoproteins and Cardiovascular HealthLipid metabolism and disordersCholesterol and Lipid Metabolism

Apolipoprotein E in lipoprotein metabolism, health and cardiovascular disease

Marais, A.David·2019·Pathology
DOI 10.1016/j.pathol.2018.11.002
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Abstract

Apolipoprotein E (apoE), a 34 kDa circulating glycoprotein of 299 amino acids, predominantly synthesised in the liver, associates with triglyceride-rich lipoproteins to mediate the clearance of their remnants after enzymatic lipolysis in the circulation. Its synthesis in macrophages initiates the formation of high density-like lipoproteins to effect reverse cholesterol transport to the liver. In the nervous system apoE forms similar lipoproteins which perform the function of distributing lipids amongst cells. ApoE accounts for much of the variation in plasma lipoproteins by three common variants (isoforms) that influence low-density lipoprotein concentration and the risk of atherosclerosis. ApoE2 generally is most favourable and apoE4 least favourable for cardiovascular and neurological health. The apoE variants relate to different amino acids at positions 112 and 158: cysteine in both for apoE2, arginine at both sites for apoE4, and respectively cysteine and arginine for apoE3 that is viewed as the wild type. Paradoxically, under metabolic stress, homozygosity for apoE2 may result in dysbetalipoproteinaemia in adults owing to impaired binding of remnant lipoproteins to the LDL receptor and related proteins as well as heparan sulphate proteoglycans. This highly atherogenic condition is also seen with other mutations in apoE, but with autosomal dominant inheritance. Mutations in apoE may also cause lipoprotein glomerulopathy. In the central nervous system apoE binds amyloid β-…

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Crossref · 10.1016/j.pathol.2018.11.002

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144 of 144 references verified0 citation errors · 0 not checkable

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  • In APOE2 (variant ε2), due to the cysteine 158 substitution, aspartic acid 154 changes its ionic interaction with arginine 150 instead of arginine 158, disrupting LDL receptor binding significantly.

    “as is reported in APOE2 (variant ε2), due to the cysteine 158 substitution, aspartic acid 154 changes its ionic interaction with arginine 150 instead of arginine 158, disrupting LDL receptor binding significantly (Marais, 2019).”

    From Clinical and genetic analysis of lipoprotein glomerulopathy patients caused by <i>APOE</i> mutations (2020) · cites this paper as Marais, 2019

  • ApoE2 association with high ApoE level is due to its decreased binding with LDL receptor, resulting in higher plasma level.

    “In the APOE region, association of ApoE2 with high ApoE level is due to its decreased binding with LDL receptor, resulting in higher plasm level.”

    From Genome-wide analysis identifies novel loci influencing plasma apolipoprotein E concentration and Alzheimer’s disease risk (2023) · cites this paper as [4]

  • ApoE4 association with lower ApoE level is more likely due to misfolding and accumulation of ApoE protein in the endoplasmic reticulum from an ionic interaction between Arg-61 in the N-terminal domain and Glu-255 in the C-terminal domain in the E4 isoform; this domain interaction is not present in the other two ApoE isoforms.

    “ii) more likely, it is the result of misfolding and accumulation of ApoE protein in endoplasmic reticulum due to an ionic interaction between Arg-61 in the N-terminal domain and Glu-255 in the C-terminal domain in the E4 isoform; this domain interaction is not present in the other two ApoE isoforms [3, 4].”

    From Genome-wide analysis identifies novel loci influencing plasma apolipoprotein E concentration and Alzheimer’s disease risk (2023) · cites this paper as [4]

  • ApoE exhibits heparin-binding activity and binds HSPGs on the surface of cells.

    “ApoE also exhibits heparin-binding activity and binds HSPGs on the surface of cells, a property that supports the capture and receptor-mediated uptake of apoE-containing lipoproteins by cells7).”

    From Impact of Apolipoprotein E Variants: A Review of Naturally Occurring Variants and Clinical Features (2025) · cites this paper as [7]

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Authors
Marais, A. D.
Affiliations
National Health Laboratory Service (ZA)
Corresponding author
Marais, A.David
ORCID
Marais, A.David
Venue
Pathology
Publisher
Elsevier BV
Published
2019-02
Volume
51
Issue
2
Pages
165-176
ISSN
0031-3025 (ISSN-L)
DOI
10.1016/j.pathol.2018.11.002
OpenAlex
W2906709963
Cited by
382
References
146
Citations by year
2026: 44 · 2025: 45 · 2024: 62 · 2023: 59 · 2022: 64 · 2021: 62 · 2020: 35 · 2019: 10 · 2018: 1
FWCI
6.06
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Pathology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
Keywords
apolipoprotein E, apolipoprotein E isoforms, lipoprotein metabolism, triglyceride-rich lipoproteins, reverse cholesterol transport, atherosclerosis, cardiovascular disease, dysbetalipoproteinemia, lipoprotein glomerulopathy, Alzheimer's disease, amyloid-beta, tau protein, docosahexaenoic acid, immune and inflammatory responses, APOE genotyping, personalized medicine, blood-brain barrier
MeSH terms
Apolipoproteins E, Cardiovascular Diseases, Health, Humans, Lipoproteins, Liver, Nervous System, Receptors, LDL, Risk Factors, Amyloid beta-Peptides, Heparan Sulfate Proteoglycans, Protein Isoforms, Dyslipidemias, Lipid Metabolism, Apolipoprotein E4, Apolipoprotein E2

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