The Binding of Apolipoprotein E to Oligomers and Fibrils of Amyloid-β Alters the Kinetics of Amyloid Aggregation
Open accessAbstract
Deposition of amyloid-β (Aβ) in Alzheimer’s disease (AD) is strongly correlated with the APOE genotype. However, the role of apolipoprotein E (apoE) in Aβ aggregation has remained unclear. Here we have used different apoE preparations, such as recombinant protein or protein isolated from cultured astrocytes, to examine the effect of apoE on the aggregation of both Aβ1–40 and Aβ1–42. The kinetics of aggregation, measured by the loss of fluorescence of tetramethylrhodamine-labeled Aβ, is shown to be dramatically slowed by the presence of substoichiometric concentrations of apoE. Using these concentrations, we conclude that apoE binds primarily to and affects the growth of oligomers that lead to the nuclei required for fibril growth. At higher apoE concentrations, the protein also binds to Aβ fibrils, resulting in fibril stabilization and a slower rate of fibril growth. The aggregation of Aβ1–40 is dependent on the apoE isoform, being the most dramatic for apoE4 and less so for apoE3 and apoE2. Our results indicate that the detrimental role of apoE4 in AD could be related to apoE-induced stabilization of the soluble but cytotoxic oligomeric forms and intermediates of Aβ, as well as fibril stabilization.
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The increased propensity of Aβ to oligomerize in the presence of APOE4 is considered a major mechanism by which APOE4 increases Alzheimer disease risk.
“and the increased propensity of Aβ to oligomerize in the presence of APOE4 is considered a major mechanism by which APOE4 increases AD risk113–116 (Fig. 2c).”
From Multifaceted roles of APOE in Alzheimer disease (2024) · cites this paper as [115]
The Discussion (page unavailable) proposes that apoE4’s detrimental effects are mediated by stabilization of toxic Aβ intermediates. It does not show that apoE4 increases Aβ’s propensity to oligomerize; it reports delayed aggregation and presents the disease mechanism as a hypothesis rather than an established major mechanism. (LLM, conf=0.86)
Experimental — accuracy not yet measuredAPOE4 is associated with increased oligomerization and deposition of Aβ in vitro and in vivo.
“APOE4 is associated with increased oligomerization and deposition of Aβ in vitro and in vivo113,115,192”
From Multifaceted roles of APOE in Alzheimer disease (2024) · cites this paper as [115]
The Discussion (page not available in our copy) reports greater Aβ deposition in the brains of people with apoE4 and in APP mouse models. The paper proposes that apoE4 stabilizes soluble Aβ oligomeric intermediates, but its in vitro results show delayed overall aggregation, not increased oligomerization and deposition in vitro. (LLM, conf=0.87)
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Cites
ApoE-Directed Therapeutics Rapidly Clear β-Amyloid and Reverse Deficits in AD Mouse Models
Cramer, P. E., Cirrito, J. R., Wesson, D. W., Lee, C. Y. D., Karlo, J. C., Zinn, A. E., Casali, B. T., Restivo, J. L., Goebel, W. D., James, M. J., et al. (2012) · Science · doi:10.1126/science.1217697 · Cited by 1,050 · see citing works
Ma, J., Yee, A., Brewer, H. B., Das, S., & Potter, H. (1994) · Nature · doi:10.1038/372092a0 · Cited by 871 · see citing works
<i>APOE</i> predicts amyloid‐beta but not tau Alzheimer pathology in cognitively normal aging
Morris, J. C., Roe, C. M., Xiong, C., Fagan, A. M., Goate, A. M., Holtzman, D. M., & Mintun, M. A. (2010) · Annals of Neurology · doi:10.1002/ana.21843 · Cited by 830 · see citing works
Self-citationapoE isoform–specific disruption of amyloid β peptide clearance from mouse brain
Deane, R., Sagare, A., Hamm, K., Parisi, M., Lane, S., Finn, M. B., Holtzman, D. M., & Zlokovic, B. V. (2008) · Journal of Clinical Investigation · doi:10.1172/jci36663 · Cited by 771 · see citing works
Self-citationApolipoprotein E structure: insights into function
Hatters, D. M., Peters-Libeu, C. A., & Weisgraber, K. H. (2006) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2006.06.008 · Cited by 583 · see citing works
Apolipoprotein E4 effects in Alzheimer’s disease are mediated by synaptotoxic oligomeric amyloid-β
Koffie, R. M., Hashimoto, T., Tai, H.-C., Kay, K. R., Serrano-Pozo, A., Joyner, D., Hou, S., Kopeikina, K. J., Frosch, M. P., Lee, V. M., et al. (2012) · Brain · doi:10.1093/brain/aws127 · Cited by 327 · see citing works
Self-citationApolipoprotein E, Especially Apolipoprotein E4, Increases the Oligomerization of Amyloid β Peptide
Hashimoto, T., Serrano-Pozo, A., Hori, Y., Adams, K. W., Takeda, S., Banerji, A. O., Mitani, A., Joyner, D., Thyssen, D. H., Bacskai, B. J., et al. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.1542-12.2012 · Cited by 294 · see citing works
Self-citationSadowski, M. J., Pankiewicz, J., Scholtzova, H., Mehta, P. D., Prelli, F., Quartermain, D., & Wisniewski, T. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0604011103 · Cited by 167 · see citing works
Tai, L. M., Bilousova, T., Jungbauer, L., Roeske, S. K., Youmans, K. L., Yu, C., Poon, W. W., Cornwell, L. B., Miller, C. A., Vinters, H. V., et al. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.442103 · Cited by 165 · see citing works
Anti-apoE immunotherapy inhibits amyloid accumulation in a transgenic mouse model of Aβ amyloidosis
Kim, J., Eltorai, A. E. M., Jiang, H., Liao, F., Verghese, P. B., Kim, J., Stewart, F. R., Basak, J. M., & Holtzman, D. M. (2012) · Journal of Experimental Medicine · doi:10.1084/jem.20121274 · Cited by 160 · see citing works
Self-citationBelinson, H., Lev, D., Masliah, E., & Michaelson, D. M. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.5633-07.2008 · Cited by 101 · see citing works
A Monomeric, Biologically Active, Full-Length Human Apolipoprotein E
Zhang, Y., Vasudevan, S., Sojitrawala, R., Zhao, W., Cui, C., Xu, C., Fan, D., Newhouse, Y., Balestra, R., Jerome, W. G., et al. (2007) · Biochemistry · doi:10.1021/bi700672v · Cited by 79 · see citing works
Flagged first, then by citations
Research works printed but not linked: 41
- Strittmatter W. J.; Saunders A. M.; Schmechel D.; Pericak-Vance M.; Enghild J.; Salvesen G. S.; Roses A. D. (1993) Apolipoprotein E: High-avidity binding to β-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc. Natl. Acad. Sci. U.S.A. 90, 1977– 1981. 8446617 PMC46003
- Corder E. H.; Saunders A. M.; Pericak-Vance M. A.; Roses A. D. (1995) There is a pathologic relationship between ApoE-ε4 and Alzheimer’s disease. Arch. Neurol. 52, 650– 651. 7619017
- Wisniewski T.; Frangione B. (1992) Apolipoprotein E: A pathological chaperone protein in patients with cerebral and systemic amyloid. Neurosci. Lett. 135, 235– 238. 1625800
- Wisniewski T.; Castano E. M.; Golabek A.; Vogel T.; Frangione B. (1994) Acceleration of Alzheimer’s fibril formation by apolipoprotein E in vitro. Am. J. Pathol. 145, 1030– 1035. 7977635 PMC1887417
- Evans K. C.; Berger E. P.; Cho C. G.; Weisgraber K. H.; Lansbury P. T. Jr. (1995) Apolipoprotein E is a kinetic but not a thermodynamic inhibitor of amyloid formation: Implications for the pathogenesis and treatment of Alzheimer disease. Proc. Natl. Acad. Sci. U.S.A. 92, 763– 767. 7846048 PMC42700
- Holtzman D. M.; Bales K. R.; Tenkova T.; Fagan A. M.; Parsadanian M.; Sartorius L. J.; Mackey B.; Olney J.; McKeel D.; Wozniak D.; Paul S. M. (2000) Apolipoprotein E isoform-dependent amyloid deposition and neuritic degeneration in a mouse model of Alzheimer’s disease. Proc. Natl. Acad. Sci. U.S.A. 97, 2892– 2897. 10694577 PMC16026
- Verghese P. B.; Castellano J. M.; Garai K.; Wang Y.; Jiang H.; Shah A.; Bu G.; Frieden C.; Holtzman D. M. (2013) ApoE influences amyloid-β (Aβ) clearance despite minimal apoE/Aβ association in physiological conditions. Proc. Natl. Acad. Sci. U.S.A. 110, E1807– E1816. 23620513 PMC3651443
- Biere A. L.; Ostaszewski B.; Stimson E. R.; Hyman B. T.; Maggio J. E.; Selkoe D. J. (1996) Amyloid β-Peptide Is Transported on Lipoproteins and Albumin in Human Plasma. J. Biol. Chem. 271, 32916– 32922. 8955133
- Fagan A. M.; Younkin L. H.; Morris J. C.; Fryer J. D.; Cole T. G.; Younkin S. G.; Holtzman D. M. (2000) Differences in the Aβ40/Aβ42 ratio associated with cerebrospinal fluid lipoproteins as a function of apolipoprotein E genotype. Ann. Neurol. 48, 201– 210. 10939571
- Namba Y.; Tomonaga M.; Kawasaki H.; Otomo E.; Ikeda K. (1991) Apolipoprotein E immunoreactivity in cerebral amyloid deposits and neurofibrillary tangles in Alzheimer’s disease and kuru plaque amyloid in Creutzfeldt-Jakob disease. Brain Res. 541, 163– 166. 2029618
- LaDu M. J.; Falduto M. T.; Manelli A. M.; Reardon C. A.; Getz G. S.; Frail D. E. (1994) Isoform-specific binding of apolipoprotein E to β-amyloid. J. Biol. Chem. 269, 23403– 23406. 8089103
- Cerf E.; Gustot A.; Goormaghtigh E.; Ruysschaert J. M.; Raussens V. (2011) High ability of apolipoprotein E4 to stabilize amyloid-β peptide oligomers, the pathological entities responsible for Alzheimer’s disease. FASEB J. 25, 1585– 1595. 21266538
- Ly S.; Altman R.; Petrlova J.; Lin Y.; Hilt S.; Huser T.; Laurence T. A.; Voss J. C. (2013) Binding of apolipoprotein E inhibits the oligomer growth of amyloid-β peptide in solution as determined by fluorescence cross-correlation spectroscopy. J. Biol. Chem. 288, 11628– 11635. 23430745 PMC3636854
- Chen J.; Li Q.; Wang J. (2011) Topology of human apolipoprotein E3 uniquely regulates its diverse biological functions. Proc. Natl. Acad. Sci. U.S.A. 108, 14813– 14818. 21873229 PMC3169138
- Peters-Libeu C. A.; Newhouse Y.; Hall S. C.; Witkowska H. E.; Weisgraber K. H. (2007) Apolipoprotein E-dipalmitoylphosphatidylcholine particles are ellipsoidal in solution. J. Lipid Res. 48, 1035– 1044. 17308333
- Garai K.; Sahoo B.; Kaushalya S. K.; Desai R.; Maiti S. (2007) Zinc lowers amyloid-β toxicity by selectively precipitating aggregation intermediates. Biochemistry 46, 10655– 10663. 17718543
- Cleary J. P.; Walsh D. M.; Hofmeister J. J.; Shankar G. M.; Kuskowski M. A.; Selkoe D. J.; Ashe K. H. (2005) Natural oligomers of the amyloid-β protein specifically disrupt cognitive function. Nat. Neurosci. 8, 79– 84. 15608634
- Jin M.; Shepardson N.; Yang T.; Chen G.; Walsh D.; Selkoe D. J. (2011) Soluble amyloid β-protein dimers isolated from Alzheimer cortex directly induce Tau hyperphosphorylation and neuritic degeneration. Proc. Natl. Acad. Sci. U.S.A. 108, 5819– 5824. 21421841 PMC3078381
- Carter D. B. (2005) The interaction of amyloid-β with ApoE. Subcell. Biochem. 38, 255– 272. 15709483
- Garai K.; Frieden C. (2013) Quantitative analysis of the time course of Aβ oligomerization and subsequent growth steps using tetramethylrhodamine-labeled Aβ. Proc. Natl. Acad. Sci. U.S.A. 110, 3321– 3326. 23401512 PMC3587211
- Garai K.; Mustafi S. M.; Baban B.; Frieden C. (2010) Structural differences between apolipoprotein E3 and E4 as measured by 19F NMR. Protein Sci. 19, 66– 74. 19904741 PMC2817840
- Garai K.; Baban B.; Frieden C. (2011) Dissociation of apoE oligomers to monomers is required for high affinity binding to phospholipid vesicles. Biochemistry 50, 2550– 2558. 21322570 PMC3088999
- Schneeweis L. A.; Koppaka V.; Lund-Katz S.; Phillips M. C.; Axelsen P. H. (2005) Structural Analysis of Lipoprotein E Particles. Biochemistry 44, 12525– 12534. 16156664
- Huang R. Y. C.; Garai K.; Frieden C.; Gross M. L. (2011) Hydrogen/Deuterium Exchange and Electron-Transfer Dissociation Mass Spectrometry Determine the Interface and Dynamics of Apolipoprotein E Oligomerization. Biochemistry 50, 9273– 9282. 21899263 PMC3202646
- Xue W. F.; Radford S. E. (2013) An imaging and systems modeling approach to fibril breakage enables prediction of amyloid behavior. Biophys. J. 105, 2811– 2819. 24359753 PMC3882454
- LaDu M. J.; Shah J. A.; Reardon C. A.; Getz G. S.; Bu G.; Hu J.; Guo L.; Van Eldik L. J. (2001) Apolipoprotein E and apolipoprotein E receptors modulate Aβ-induced glial neuroinflammatory responses. Neurochem. Int. 39, 427– 434. 11578778
- Bien-Ly N.; Gillespie A. K.; Walker D.; Yoon S. Y.; Huang Y. (2012) Reducing human apolipoprotein E levels attenuates age-dependent Aβ accumulation in mutant human amyloid precursor protein transgenic mice. J. Neurosci. 32, 4803– 4811. 22492035 PMC3433173
- Lee J.; Culyba E. K.; Powers E. T.; Kelly J. W. (2011) Amyloid-β forms fibrils by nucleated conformational conversion of oligomers. Nat. Chem. Biol. 7, 602– 609. 21804535 PMC3158298
- Knowles T. P.; Waudby C. A.; Devlin G. L.; Cohen S. I.; Aguzzi A.; Vendruscolo M.; Terentjev E. M.; Welland M. E.; Dobson C. M. (2009) An analytical solution to the kinetics of breakable filament assembly. Science 326, 1533– 1537. 20007899
- Cohen S. I.; Linse S.; Luheshi L. M.; Hellstrand E.; White D. A.; Rajah L.; Otzen D. E.; Vendruscolo M.; Dobson C. M.; Knowles T. P. (2013) Proliferation of amyloid-β42 aggregates occurs through a secondary nucleation mechanism. Proc. Natl. Acad. Sci. U.S.A. 110, 9758– 9763. 23703910 PMC3683769
- Xue W.-F.; Hellewell A. L.; Gosal W. S.; Homans S. W.; Hewitt E. W.; Radford S. E. (2009) Fibril Fragmentation Enhances Amyloid Cytotoxicity. J. Biol. Chem. 284, 34272– 34282. 19808677 PMC2797196
- Webster S.; Rogers J. (1996) Relative efficacies of amyloid β peptide (Aβ) binding proteins in Aβ aggregation. J. Neurosci. Res. 46, 58– 66. 8892106
- Chauhan A.; Pirttila T.; Mehta P.; Chauhan V. P.; Wisniewski H. M. (1996) Effect of cerebrospinal fluid from normal and Alzheimer’s patients with different apolipoprotein E phenotypes on in vitro aggregation of amyloid β-protein. J. Neurol. Sci. 141, 54– 58. 8880693
- Beffert U.; Poirier J. (1998) ApoE associated with lipid has a reduced capacity to inhibit β-amyloid fibril formation. NeuroReport 9, 3321– 3323. 9831470
- Castano E. M.; Prelli F.; Wisniewski T.; Golabek A.; Kumar R. A.; Soto C.; Frangione B. (1995) Fibrillogenesis in Alzheimer’s disease of amyloid β peptides and apolipoprotein E. Biochem. J. 306(Part 2), 599– 604. 7534068 PMC1136559
- Bitan G.; Lomakin A.; Teplow D. B. (2001) Amyloid β-protein oligomerization: Prenucleation interactions revealed by photo-induced cross-linking of unmodified proteins. J. Biol. Chem. 276, 35176– 35184. 11441003
- Bernstein S. L.; Dupuis N. F.; Lazo N. D.; Wyttenbach T.; Condron M. M.; Bitan G.; Teplow D. B.; Shea J. E.; Ruotolo B. T.; Robinson C. V.; Bowers M. T. (2009) Amyloid-β protein oligomerization and the importance of tetramers and dodecamers in the aetiology of Alzheimer’s disease. Nat. Chem. 1, 326– 331. 20703363 PMC2918915
- Strittmatter 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) Binding of human apolipoprotein E to synthetic amyloid β peptide: Isoform-specific effects and implications for late-onset Alzheimer disease. Proc. Natl. Acad. Sci. U.S.A. 90, 8098– 8102. 8367470 PMC47295
- Tanaka M.; Vedhachalam C.; Sakamoto T.; Dhanasekaran P.; Phillips M. C.; Lund-Katz S.; Saito H. (2006) Effect of Carboxyl-Terminal Truncation on Structure and Lipid Interaction of Human Apolipoprotein E4. Biochemistry 45, 4240– 4247. 16566598
- Hoshino T.; Mahmood I.; Mori K.; Matsuzaki K. (2013) Binding and Aggregation Mechanism of Amyloid β-Peptides onto the GM1 Ganglioside-Containing Lipid Membrane. J. Phys. Chem. B 117, 8085– 8094. 23688073
- Frieden C.; Garai K. (2012) Structural differences between apoE3 and apoE4 may be useful in developing therapeutic agents for Alzheimer’s disease. Proc. Natl. Acad. Sci. U.S.A. 109, 8913– 8918. 22615372 PMC3384159
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Self-citation
- Authors
- Garai, K., Verghese, P. B., Baban, B., Holtzman, D. M., & Frieden, C.
- Affiliations
- Tata Institute of Fundamental Research (IN)
- Washington University in St. Louis (US)
- Corresponding author
- Frieden, Carl
- Venue
- Biochemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2014-09-10
- Volume
- 53
- Issue
- 40
- Pages
- 6323-6331
- ISSN
- 0006-2960 (ISSN-L)
- 1520-4995
- PMC
- PMC4196732
- OpenAlex
- W2094007252
- Cited by
- 145
- References
- 12
- Citations by year
- 2026: 16 · 2025: 16 · 2024: 17 · 2023: 14 · 2022: 10 · 2021: 6 · 2020: 9 · 2019: 16 · 2018: 8 · 2017: 14 · 2016: 9 · 2015: 8 · 2014: 2
- FWCI
- 7.33
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Biochemistry (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (R01 AG13956)
- BrightFocus Foundation
- Cure Alzheimer's Fund
- 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, amyloid-beta, oligomers, fibrils, APOE isoforms, APOE ε4, Alzheimer's disease, Aβ40, amyloid-beta 42, protein-protein binding, astrocytes
- MeSH terms
- Amyloid, Apolipoproteins E, Humans, Kinetics, Peptide Fragments, Protein Binding, Amyloid beta-Peptides, Protein Structure, Quaternary, Protein Multimerization, Protein Stability
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