Mechanisms linking apolipoprotein E isoforms with cardiovascular and neurological diseases.
Abstract
Purpose of review The purpose of this review is to provide insights into recent advances in mechanisms linking apolipoprotein (apo) E isoforms to cardiovascular and neurological diseases. Recent findings Human apoE has three common isoforms (apoE2, apoE3, and apoE4) with different structural and biophysical properties and different effects on lipid and neuronal homeostasis. ApoE is a protein constituent of different plasma lipoproteins and serves as a high-affinity ligand for several receptors. By interacting with its receptors, apoE mediates the clearance of different lipoproteins from the circulation. Absence or structural mutations of apoE cause significant disorders in lipid metabolism and cardiovascular disease. ApoE also has significant roles in neurobiology. ApoE4 is the major known genetic risk factor for Alzheimer's disease. It increases the occurrence and lowers the age of onset of Alzheimer's disease. ApoE4 carriers account for 65-80% of all Alzheimer's disease cases, highlighting the importance of apoE4 in Alzheimer's disease pathogenesis. ApoE4 has both amyloid beta-dependent and amyloid beta-independent roles in Alzheimer's disease pathogenesis. Summary Emerging data suggest that apoE isoforms, with their multiple cellular origins and multiple structural and biophysical properties, contribute to cardiovascular and neurological diseases by interacting with different factors through various pathways.
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Differences in function and disease predisposition are established between apoE3 and apoE2, although these two variants differ only at a single amino acid at position 158.
“Similarly, differences in function and disease predisposition are established between apoE3 and apoE2 although these two variants differ only at a single amino acid at position 158 [65], [72], [74].”
From Biophysical Analysis of Apolipoprotein E3 Variants Linked with Development of Type III Hyperlipoproteinemia (2011) · cites this paper as [74]
The finding that rare pathogenic mutations in the N-terminal domain of apoE3 affect thermodynamic stability parameters of the full-length molecule is consistent with the well established effects of common apoE polymorphisms.
“In this context, the finding that rare pathogenic mutations in the N-terminal domain of apoE3 affect thermodynamic stability parameters of the full-length molecule is consistent with the well established effects of common apoE polymorphisms that are under intense scrutiny due to their role in the pathogenesis of cardiovascular and Alzheimer's disease [45], [74].”
From Biophysical Analysis of Apolipoprotein E3 Variants Linked with Development of Type III Hyperlipoproteinemia (2011) · cites this paper as [74]
ApoE polymorphisms are associated with other lipid abnormalities and neurological disorders such as Alzheimer disease.
“Moreover, apoE polymorphisms are associated with other lipid abnormalities and neurological disorders such as Alzheimer disease (3, 8, 9 ) .”
From Automated multiplex LC-MS/MS assay for quantifying serum apolipoproteins A-I, B, C-I, C-II, C-III, and E with qualitative apolipoprotein E phenotyping (2016) · cites this paper as [9]
ApoE is a determinant of CVD risk and atherosclerosis.
“Similarly, apoE is a determinant of CVD risk and atherosclerosis.”
From Automated multiplex LC-MS/MS assay for quantifying serum apolipoproteins A-I, B, C-I, C-II, C-III, and E with qualitative apolipoprotein E phenotyping (2016) · cites this paper as [9]
A standard tool for diagnosing dysbetalipoproteinemia is apoE phenotyping on the basis of immunostaining of 3 major isoforms (apoE2, apoE3, and apoE4) or apoE genotyping.
“A standard tool for diagnosing dysbetalipoproteinemia is apoE phenotyping on the basis of immunostaining of 3 major isoforms (apoE2, apoE3, and apoE4) or apoE genotyping (3, 8, 9 ) .”
From Automated multiplex LC-MS/MS assay for quantifying serum apolipoproteins A-I, B, C-I, C-II, C-III, and E with qualitative apolipoprotein E phenotyping (2016) · cites this paper as [9]
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- Authors
- Huang, Y.
- Affiliations
- Gladstone Institutes (US)
- Corresponding author
- Huang, Yadong
- ORCID
- Huang, Yadong
- Venue
- Current Opinion in Lipidology
- Published
- 2010-08
- Volume
- 21
- Issue
- 4
- Pages
- 337-345
- ISSN
- 0957-9672 (ISSN-L)
- OpenAlex
- W2077090804
- Cited by
- 82
- References
- 18
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 1 · 2023: 5 · 2022: 3 · 2021: 3 · 2020: 4 · 2019: 3 · 2018: 1 · 2017: 6 · 2016: 8 · 2015: 5 · 2014: 5 · 2013: 7 · 2012: 13
- FWCI
- 1.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Opinion in Lipidology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (P01AG022074)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- apolipoprotein E isoforms, APOE ε4, APOE2, APOE3, Alzheimer's disease, cardiovascular disease, lipid metabolism, lipoprotein clearance, apoE receptors, amyloid-beta, neurobiology, genetic risk factors
- MeSH terms
- Animals, Apolipoproteins E, Cardiovascular Diseases, Humans, Nervous System Diseases, Amyloid beta-Peptides, Protein Isoforms, Lipid Metabolism
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