Interaction of Nascent ApoE2, ApoE3, and ApoE4 Isoforms Expressed in Mammalian Cells with Amyloid Peptide β (1−40). Relevance to Alzheimer's Disease
Abstract
Population studies have established that one of the common isoforms of apolipoprotein E, the apoE4, is associated with higher incidence and earlier age of onset of late onset familial Alzheimer's disease (AD), whereas apoE2 may have the opposite effect. The apoE3 and apoE4 isoforms were shown to display different binding reactivities with amyloid beta peptide (Abeta) and tau protein in vitro. On the basis of these findings, it has been proposed that the apoE isoforms may modulate positively or negatively the formation of either the neurofibrillary tangles or the amyloid deposits in the brain of patients with AD. To study the interaction of Abeta with nascent apoE isoforms we have expressed their cDNAs in baby hamster kidney (BHK-21) cells using the Semliki Forest Virus expression system. Analysis of the secreted apoE by one- and two-dimensional gel electrophoresis and immunoblotting showed that the nascent apoE is heavily modified with carbohydrate chains containing sialic acid. A dimeric form of apoE is formed with apoE2 and apoE3 but not with apoE4 isoforms. Analysis of the interaction of nascent apoE2, apoE3, and apoE4 produced by BHK-21 cells with Abeta (1-40) under physiological conditions (pH 7.4, 37 degrees C) showed that the efficiency of the apoE monomer-Abeta complex formation follows the order apoE2 > apoE3 >> apoE4. In addition, the apoE2 dimer formed a complex with Abeta more efficiently than the apoE3 dimer. The isoform-specific differences in binding were tempe…
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Several in vitro studies have demonstrated that lipidated apoE2 and apoE3 bind Aβ with greater affinity compared to apoE4.
“Several in vitro studies have demonstrated that lipidated apoE2 and apoE3 bind Aβ with greater affinity compared to apoE4 (39, 51-54).”
From Human ApoE isoforms differentially regulate brain amyloid-β peptide clearance (2011) · cites this paper as [53]
Aβ42 uptake is likely facilitated by APOE-bound Aβ42 clearance, with complex formation being genotype dependent (E2 > E3 > E4).
“which is likely facilitated by APOE-bound Aβ42 clearance; a complex formation that is genotype dependent (E2 > E3 > E4) (Aleshkov et al., 1997).”
From APOE2, E3, and E4 differentially modulate cellular homeostasis, cholesterol metabolism, and inflammatory response in isogenic iPSC-derived astrocytes (2022) · cites this paper as Aleshkov et al., 1997
Subsequent studies reported that lipid-associated apoE2 and apoE3 formed SDS-stable complexes with Aβ to a much greater extent than apoE4.
“However, subsequent studies reported that lipid-associated apoE2 and apoE3 formed SDS-stable complexes with Aβ to a much greater extent than apoE4 (Aleshkov et al., 1997; LaDu et al., 1994; Yang et al., 1997).”
From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Aleshkov et al., 1997
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- Authors
- Aleshkov, S., Abraham, C. R., & Zannis, V. I.
- Affiliations
- Boston University (US)
- Venue
- Biochemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 1997-08-26
- Volume
- 36
- Issue
- 34
- Pages
- 10571-10580
- ISSN
- 0006-2960 (ISSN-L)
- 1520-4995
- OpenAlex
- W2017524770
- Cited by
- 138
- References
- 4
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 4 · 2023: 6 · 2022: 7 · 2021: 3 · 2020: 7 · 2019: 2 · 2017: 5 · 2016: 4 · 2015: 5 · 2014: 5 · 2013: 3 · 2012: 6
- FWCI
- 4.62
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ag012717-03)
- National Institute on Aging (AG-12717)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- apolipoprotein E isoforms, APOE2, APOE3, APOE ε4, amyloid-beta, Aβ40, Alzheimer's disease, sialic acid glycosylation, temperature dependence of binding, apoE secretion, amyloid clearance
- MeSH terms
- Alzheimer Disease, Animals, Apolipoproteins E, Cell Line, Electrophoresis, Polyacrylamide Gel, Cricetinae, Humans, Peptide Fragments, Protein Binding, Protein Conformation, Recombinant Proteins, Temperature, Immunoblotting, Electrophoresis, Gel, Two-Dimensional, Amyloid beta-Peptides, Baculoviridae, tau Proteins, Dimerization, Apolipoprotein E3, Apolipoprotein E4, Apolipoprotein E2
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