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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]
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In the citing paper
“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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Corder, E. H., Saunders, A. M., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Small, G. W., Roses, A. D., Haines, J. L., & Pericak-Vance, M. A. (1993) · Science · doi:10.1126/science.8346443 · Cited by 9,429
Strittmatter, W. J., Saunders, A. M., Schmechel, D., Pericak-Vance, M., Enghild, J., Salvesen, G. S., & Roses, A. D. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.5.1977 · Cited by 4,268
Association of apolipoprotein E allele ϵ4 with late‐onset familial and sporadic Alzheimer's disease
Saunders, A. M., Strittmatter, W. J., Schmechel, D., St. George-Hyslop, P. H., Pericak-Vance, M. A., Joo, S. H., Rosi, B. L., Gusella, J. F., Crapper-MacLachlan, D. R., Alberts, M. J., et al. (1993) · Neurology · doi:10.1212/wnl.43.8.1467 · Cited by 3,786
Diffusible, nonfibrillar ligands derived from Aβ 1–42 are potent central nervous system neurotoxins
Lambert, M. P., Barlow, A. K., Chromy, B. A., Edwards, C., Freed, R., Liosatos, M., Morgan, T. E., Rozovsky, I., Trommer, B., Viola, K. L., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.11.6448 · Cited by 3,506
Isolation and quantification of soluble Alzheimer's β-peptide from biological fluids
Seubert, P., Vigo-Pelfrey, C., Esch, F., Lee, M., Dovey, H., Davis, D., Sinha, S., Schiossmacher, M., Whaley, J., Swindlehurst, C., et al. (1992) · Nature · doi:10.1038/359325a0 · Cited by 1,731
Schmechel, D. E., Saunders, A. M., Strittmatter, W. J., Crain, B. J., Hulette, C. M., Joo, S. H., Pericak-Vance, M. A., Goldgaber, D., & Roses, A. D. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.20.9649 · Cited by 1,525
Production of the Alzheimer Amyloid β Protein by Normal Proteolytic Processing
Shoji, M., Golde, T. E., Ghiso, J., Cheung, T. T., Estus, S., Shaffer, L. M., Cai, X.-D., McKay, D. M., Tintner, R., Frangione, B., et al. (1992) · Science · doi:10.1126/science.1439760 · Cited by 1,447
Self-citationStrittmatter, W. J., Weisgraber, K. H., Huang, D. Y., Dong, L. M., Salvesen, G. S., Pericak-Vance, M., Schmechel, D., Saunders, A. M., Goldgaber, D., & Roses, A. D. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.17.8098 · Cited by 1,363
Namba, Y., Tomonaga, M., Kawasaki, H., Otomo, E., & Ikeda, K. (1991) · Brain Research · doi:10.1016/0006-8993(91)91092-f · Cited by 1,157
Apolipoprotein E in sporadic Alzheimer's disease: Allelic variation and receptor interactions
William Rebeck, G., Reiter, J. S., Strickland, D. K., & Hyman, B. T. (1993) · Neuron · doi:10.1016/0896-6273(93)90070-8 · Cited by 1,107
Lack of apolipoprotein E dramatically reduces amyloid β-peptide deposition
Bales, K. R., Verina, T., Dodel, R. C., Du, Y., Altstiel, L., Bender, M., Hyslop, P., Johnstone, E. M., Little, S. P., Cummins, D. J., et al. (1997) · Nature Genetics · doi:10.1038/ng1197-263 · Cited by 830
Apolipoprotein E: a pathological chaperone protein in patients with cerebral and systemic amyloid
Wisniewski, T., & Frangione, B. (1992) · Neuroscience Letters · doi:10.1016/0304-3940(92)90444-c · Cited by 802
Self-citationDifferential Effects of Apolipoproteins E3 and E4 on Neuronal Growth in Vitro
Nathan, B. P., Bellosta, S., Sanan, D. A., Weisgraber, K. H., Mahley, R. W., & Pitas, R. E. (1994) · Science · doi:10.1126/science.8171342 · Cited by 795
Miyata, M., & Smith, J. D. (1996) · Nature Genetics · doi:10.1038/ng0996-55 · Cited by 735
Self-citationAstrocytes synthesize apolipoprotein E and metabolize apolipoprotein E-containing lipoproteins
Pitas, R. E., Boyles, J. K., Lee, S. H., Foss, D., & Mahley, R. W. (1987) · Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism · doi:10.1016/0005-2760(87)90295-5 · Cited by 693
Zannis, V. I., & Breslow, J. L. (1981) · Biochemistry · doi:10.1021/bi00507a059 · Cited by 563
Isoform-specific binding of apolipoprotein E to beta-amyloid.
LaDu, M. J., Falduto, M. T., Manelli, A. M., Reardon, C. A., Getz, G. S., & Frail, D. E. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)31529-6 · Cited by 540
Self-citationNäslund, J., Schierhorn, A., Hellman, U., Lannfelt, L., Roses, A. D., Tjernberg, L. O., Silberring, J., Gandy, S. E., Winblad, B., & Greengard, P. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.18.8378 · Cited by 468
Matz, C. E., & Jonas, A. (1982) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)34756-2 · Cited by 440
Rapid Communication: Characterization of β‐Amyloid Peptide from Human Cerebrospinal Fluid
Vigo‐Pelfrey, C., Lee, D., Keim, P., Lieberburg, I., & Schenk, D. B. (1993) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1993.tb09841.x · Cited by 385
Astrocytic apolipoprotein E mRNA and GFAP mRNA in hippocampus after entorhinal cortex lesioning
Poirier, J., Hess, M. A., May, P. C., & Finch, C. E. (1991) · Molecular Brain Research · doi:10.1016/0169-328x(91)90111-a · Cited by 382
Oda, T., Wals, P., Osterburg, H. H., Johnson, S. A., Pasinetti, G. M., Morgan, T. E., Rozovsky, I., Stine, W. B., Snyder, S. W., Holzman, T. F., et al. (1995) · Experimental Neurology · doi:10.1006/exnr.1995.1080 · Cited by 352
Holtzman, D. M., Bales, K. R., Wu, S., Bhat, P., Parsadanian, M., Fagan, A. M., Chang, L. K., Sun, Y., & Paul, S. M. (1999) · Journal of Clinical Investigation · doi:10.1172/jci6179 · Cited by 349
Presence of soluble amyloid β–peptide precedes amyloid plaque formation in Down's syndrome
Teller, J. K., Russo, C., DeBusk, L. M., Angelini, G., Zaccheo, D., Dagna-Bricarelli, F., Scartezzini, P., Bertolini, S., Mann, D. M. A., Tabaton, M., et al. (1996) · Nature Medicine · doi:10.1038/nm0196-93 · Cited by 326
Nascent astrocyte particles differ from lipoproteins in CSF
LaDu, M. J., Gilligan, S. M., Lukens, J. R., Cabana, V. G., Reardon, C. A., Van Eldik, L. J., & Holtzman, D. M. (1998) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1998.70052070.x · Cited by 285
Self-citationInnerarity, T. L., Pitas, R. E., & Mahley, R. W. (1979) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)50713-4 · Cited by 246
[26] Electron microscopy of negatively stained lipoproteins
Forte, T. M., & Nordhausen, R. W. (1986) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(86)28086-6 · Cited by 233
Apolipoprotein E: Binding to Soluble Alzheimer′s β-Amyloid
Wisniewski, T., Golabek, A., Matsubara, E., Ghiso, J., & Frangione, B. (1993) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1993.1423 · Cited by 212
Self-citationNäslund, J., Thyberg, J., Tjernberg, L. O., Wernstedt, C., Karlström, A. R., Bogdanović, N., Gandy, S., Lannfelt, L., Terenius, L. Y., & Nordstedt, C. (1995) · Neuron · doi:10.1016/0896-6273(95)90079-9 · Cited by 197
Purification of Apolipoprotein E Attenuates Isoform-specific Binding to β-Amyloid
LaDu, M. J., Pederson, T. M., Frail, D. E., Reardon, C. A., Getz, G. S., & Falduto, M. T. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.16.9039 · Cited by 189
Self-citationIs Alzheimer's disease an apolipoprotein E amyloidosis?
Wisniewski, T., Lalowski, M., Golabek, A., Frangione, B., & Vogel, T. (1995) · The Lancet · doi:10.1016/s0140-6736(95)90701-7 · Cited by 155
Self-citationCharacterization of Apolipoprotein J-Alzheimer's Aβ Interaction
Matsubara, E., Frangione, B., & Ghiso, J. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.13.7563 · Cited by 153
Self-citationKoudinov, A. R., Matsubara, E., Frangione, B., & Ghiso, J. A. (1994) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1994.2788 · Cited by 141
Self-citationAleshkov, S., Abraham, C. R., & Zannis, V. I. (1997) · Biochemistry · doi:10.1021/bi9626362 · Cited by 138
Biology of Aβ Amyloid in Alzheimer's Disease
Wisniewski, T., Ghiso, J., & Frangione, B. (1997) · Neurobiology of Disease · doi:10.1006/nbdi.1997.0147 · Cited by 134
Self-citationSoluble Amyloid β-Protein Is a Marker of Alzheimer Amyloid in Brain But Not in Cerebrospinal Fluid
Tabaton, M., Nunzi, M. G., Xue, R., Usiak, M., AUTILIO‐GAMBETTI, L., & Gambetti, P. L. (1994) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1994.1634 · Cited by 126
[9] Delipidation of plasma lipoproteins
Osborne, J. C. (1986) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(86)28069-6 · Cited by 118
Behavior of human apolipoprotein E in aqueous solutions and at interfaces.
Yokoyama, S., Kawai, Y., Tajima, S., & Yamamoto, A. (1985) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)36247-6 · Cited by 114
Smith, J. D., Melián, A., Leff, T., & Breslow, J. L. (1988) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)68477-7 · Cited by 114
Self-citationFunctional and structural properties of lipid-associated apolipoprotein J (clusterin)
CALERO, M., TOKUDA, T., ROSTAGNO, A., KUMAR, A., ZLOKOVIC, B., FRANGIONE, B., & GHISO, J. (1999) · Biochemical Journal · doi:10.1042/bj3440375 · Cited by 98
Self-citationAssociation of human, rat, and rabbit apolipoprotein E with ?-amyloid
LaDu, M. J., Lukens, J. R., Reardon, C. A., & Getz, G. S. (1997) · Journal of Neuroscience Research · doi:10.1002/(sici)1097-4547(19970701)49:1 · Cited by 92
Self-citationAlzheimer's soluble amyloid β is a normal component of human urine
Ghiso, J. A., Calero, M., Matsubara, E., Governale, S., Chuba, J. V., Beavis, R. C., Wısnıewskı, T., & Frangione, B. (1997) · FEBS Letters · doi:10.1016/s0014-5793(97)00400-6 · Cited by 90
Self-citationZhou, Z., Smith, J. D., Greengard, P., & Gandy, S. (1996) · Molecular Medicine · doi:10.1007/bf03401614 · Cited by 73
Self-citationZhou, Z., Smith, J. D., Greengard, P., & Gandy, S. (1996) · PubMed Central · Cited by 71
Self-citationDeposits of Aβ fibrils are not toxic to cortical and hippocampal neurons in vitro
Wujek, J. R., Dority, M. D., Frederickson, R. C. A., & Brunden, K. R. (1996) · Neurobiology of Aging · doi:10.1016/0197-4580(95)02020-9 · Cited by 36
Aleshkov, S. B., Li, X., Lavrentiadou, S. N., & Zannis, V. I. (1999) · Biochemistry · doi:10.1021/bi982002q · Cited by 30
Chacko, G. K., Mahlberg, F. H., & Johnson, W. J. (1988) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)38537-0 · Cited by 26
Yokoyama, S. (1990) · Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism · doi:10.1016/0005-2760(90)90266-z · Cited by 19
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Research works printed but not linked: 1
- Rebeck, G. W. and Hyman. B. T. (1999) Lipoprotein receptors in brain. In Clusterin in Normal Brain Functions and during Neurodegeneration (Finch, C. E., ed.), pp. 49-59, R. G. Landes Co., Austin 45
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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
Self-citationDeMattos, R. B., Bales, K. R., Cummins, D. J., Dodart, J.-C., Paul, S. M., & Holtzman, D. M. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.151261398 · Cited by 1,298
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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