The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
Lipidation of apolipoprotein E influences its isoform-specific interaction with Alzheimer's amyloid β peptides
Open accessAbstract
The inheritance of the apolipoprotein E (apoE) ϵ4 allele is a prevailing risk factor for sporadic and familial Alzheimer's disease (AD). ApoE isoforms bind directly to Alzheimer's amyloid β (Aβ) peptides both in vitro and in vivo. Recent studies suggest that association of apoE with lipids may modulate its interaction with Aβ. We examined the binding of lipid-associated and delipidated apoE3 and apoE4 isoforms to Aβ utilizing a solid-phase binding assay and estimated the dissociation constants for the interaction of various apoE and Aβ species. Using native apoE isoforms from stably transfected RAW 264 and human embryonic kidney 293 cells, apoE3 had greater affinity than apoE4 for both Aβ1-40 and Aβ1-42. Delipidation of apoE decreased its affinity for Aβ peptides by 5-10-fold and abolished the isoform-specificity. Conversely, incorporation of apoE isoforms produced by baculovirus-infected Sf9 cells into reconstituted human high-density-lipoprotein lipoparticles restored the affinity values for Aβ peptides and resulted in preferential binding of apoE3. The data demonstrate that native lipid-associated apoE3 binds to Aβ peptides with 2-3-fold higher affinity than lipid-associated apoE4. Since the isoforms' binding efficiency correlate inversely with the risk of developing late-onset AD, the results suggest a possible involvement of apoE3 in the clearance or routing out of Aβ from the central nervous system as one of the mechanisms underlying the pathology of the disease.
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“Increased levels of ApoE and lipidation of ApoE increase the intra-and extracellular microglial degradation of Ab 1 -42 by increasing the interaction between ApoE and Ab 1 -42 (15).”
From SUCLG2 identified as both a determinator of CSF Aβ1–42 levels and an attenuator of cognitive decline in Alzheimer's disease (2014) · cites this paper as [15]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“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 [54]
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“Most studies demonstrate that the efficiency of complex formation between lipidated apoE and Aβ follows the order of apoE2 > apoE3 ≫ apoE4 (Tokuda et al., 2000).”
From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Tokuda et al., 2000
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“studies have demonstrated that apoE4 does not clear plaques or soluble Aβ as well as apoE3 [45, 46].”
From Inhibition of ACAT as a Therapeutic Target for Alzheimer's Disease Is Independent of ApoE4 Lipidation (2023) · cites this paper as [45]
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“High-affinity in vitro binding of A b to a 2M and to lipidated apoE3 and apoE4, and a lower-affinity binding to delipidated apoE isoforms has been well documented (23, 70).”
From Clearance of Alzheimer’s amyloid-β1-40 peptide from brain by LDL receptor–related protein-1 at the blood-brain barrier (2000) · cites this paper as [70]
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Association of apolipoprotein E allele ϵ4 with late‐onset familial and sporadic Alzheimer's disease
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Diffusible, nonfibrillar ligands derived from Aβ 1–42 are potent central nervous system neurotoxins
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Isolation and quantification of soluble Alzheimer's β-peptide from biological fluids
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Production of the Alzheimer Amyloid β Protein by Normal Proteolytic Processing
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Cited by
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Amyloid Precursor Protein Processing and Alzheimer's Disease
O'Brien, R. J., & Wong, P. C. (2011) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-061010-113613 · Cited by 2,061
The role of apolipoprotein E in Alzheimer's disease
Kim, J., Basak, J. M., & Holtzman, D. M. (2009) · Neuron · doi:10.1016/j.neuron.2009.06.026 · Cited by 1,661
Shibata, M., Yamada, S., Kumar, S. R., Calero, M., Bading, J., Frangione, B., Holtzman, D. M., Miller, C. A., Strickland, D. K., Ghiso, J., et al. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10498 · Cited by 1,413
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Human ApoE isoforms differentially regulate brain amyloid-β peptide clearance
Castellano, J. M., Kim, J., Stewart, F. R., Jiang, H., DeMattos, R. B., Patterson, B. W., Fagan, A. M., Morris, J. C., Mawuenyega, K. G., Cruchaga, C., et al. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002156 · Cited by 1,242
“Several in vitro studies have demonstrated that lipidated apoE2 and apoE3 bind Aβ with greater affinity compared to apoE4 (39, 51-54).”
Metadata
- Authors
- TOKUDA, T., CALERO, M., MATSUBARA, E., VIDAL, R., KUMAR, A., PERMANNE, B., ZLOKOVIC, B., SMITH, J. D., LADU, M. J., ROSTAGNO, A., FRANGIONE, B., & GHISO, J.
- Affiliations
- New York University (US)
- Gunma University (JP)
- Department of Pathology, New York University School of Medicine, 550 First Avenue, New York, NY 10016, U.S.A.
- Department of Neurological Surgery, USC School of Medicine, Los Angeles, CA 90033, U.S.A.
- Rockefeller University (US)
- ENH Research Institute, Evanston, IL 60201, U.S.A.
- Corresponding author
- TOKUDA, Takahiko
- CALERO, Miguel
- KUMAR, Asok
- PERMANNE, Bruno
- ROSTAGNO, Agueda
- FRANGIONE, Blas
- GHISO, Jorge
- ORCID
- Venue
- Biochemical Journal
- Publisher
- Portland Press Ltd.
- Published
- 2000-05-23
- Volume
- 348
- Issue
- 2
- Pages
- 359-365
- ISSN
- 0264-6021 (ISSN-L)
- 1470-8728
- PMC
- PMC1221074
- OpenAlex
- W2131975162
- Cited by
- 272
- References
- 47
- Citations by year
- 2026: 10 · 2025: 7 · 2024: 12 · 2023: 6 · 2022: 14 · 2021: 10 · 2020: 15 · 2019: 14 · 2018: 6 · 2017: 13 · 2016: 12 · 2015: 10 · 2014: 20 · 2013: 15 · 2012: 14
- FWCI
- 4.50
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Biochemical Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (P01AG010491, AG10491, AG05891)
- National Institute of Neurological Disorders and Stroke (NS 38777, R01NS038777)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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, APOE3, APOE ε4, Alzheimer's disease, amyloid-beta, lipid modification, delipidation, high-density lipoprotein, amyloid clearance
- MeSH terms
- Animals, Apolipoproteins E, Cell Line, Humans, Kidney, Kinetics, Macrophages, Transfection, Amyloid beta-Peptides, Spodoptera, Protein Isoforms, Mice, Apolipoprotein E3, Apolipoprotein E4
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