The DOI matches its Crossref record; 85 of the 87 references it cites were found in a registry or an index.
A Synthetic Peptide Blocking the Apolipoprotein E/β-Amyloid Binding Mitigates β-Amyloid Toxicity and Fibril Formation in Vitro and Reduces β-Amyloid Plaques in Transgenic Mice
Open accessAbstract
Alzheimer's disease (AD) is associated with accumulation of beta-amyloid (Abeta). A major genetic risk factor for sporadic AD is inheritance of the apolipoprotein (apo) E4 allele. ApoE can act as a pathological chaperone of Abeta, promoting its conformational transformation from soluble Abeta into toxic aggregates. We determined if blocking the apoE/Abeta interaction reduces Abeta load in transgenic (Tg) AD mice. The binding site of apoE on Abeta corresponds to residues 12 to 28. To block binding, we synthesized a peptide containing these residues, but substituted valine at position 18 to proline (Abeta12-28P). This changed the peptide's properties, making it non-fibrillogenic and non-toxic. Abeta12-28P competitively blocks binding of full-length Abeta to apoE (IC50 = 36.7 nmol). Furthermore, Abeta12-28P reduces Abeta fibrillogenesis in the presence of apoE, and Abeta/apoE toxicity in cell culture. Abeta12-28P is blood-brain barrier-permeable and in AD Tg mice inhibits Abeta deposition. Tg mice treated with Abeta12-28P for 1 month had a 63.3% reduction in Abeta load in the cortex (P = 0.0043) and a 59.5% (P = 0.0087) reduction in the hippocampus comparing to age-matched control Tg mice. Antibodies against Abeta were not detected in sera of treated mice; therefore the observed therapeutic effect of Abeta12-28P cannot be attributed to an antibody clearance response. Our experiments demonstrate that compounds blocking the interaction between Abeta and its pathological chaperones may be beneficial for treatment of beta-amyloid deposition in AD.
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“The ApoE/Ab binding was blocked with Ab12-28P, which is a nontoxic, synthetic peptide modified for increased blood-brain-barrier (BBB) permeability and extended serum half-life.16”
From Blocking the Interaction between Apolipoprotein E and Aβ Reduces Intraneuronal Accumulation of Aβ and Inhibits Synaptic Degeneration (2013) · cites this paper as [16]
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“As previously reported, the toxicity of Aβ at micromolar concentration was a potential stumbling block in a recent study.18”
From Amyloid Plaque Imaging with a Targeted MRI Contrast Agent in a Transgenic Mouse Model of Alzheimer’s Disease (2022) · cites this paper as [18]
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“To exert its promoting effect on Aβ aggregation and brain deposition, apoE directly interacts with Aβ, binding to its amino-acid residues 12–28 [11,12].”
From Blocking the apoE/Aβ interaction ameliorates Aβ-related pathology in APOE ε2 and ε4 targeted replacement Alzheimer model mice (2014) · cites this paper as [12]
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“Ab12-28P is a nontoxic synthetic peptide that was modified for in vivo application, and its BBB permeability was previously evaluated and reported.16”
From Blocking the Interaction between Apolipoprotein E and Aβ Reduces Intraneuronal Accumulation of Aβ and Inhibits Synaptic Degeneration (2013) · cites this paper as [16]
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Cites
Amyloid oligomers exacerbate tau pathology in a mouse model of tauopathy
Selenica, M.-L. B., Brownlow, M., Jimenez, J. P., Lee, D. C., Pena, G., Dickey, C. A., Gordon, M. N., & Morgan, D. (2013) · Neurodegenerative Diseases · doi:10.1159/000337230 · Cited by 10,359
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
Correlative Memory Deficits, Aβ Elevation, and Amyloid Plaques in Transgenic Mice
Hsiao, K., Chapman, P., Nilsen, S., Eckman, C., Harigaya, Y., Younkin, S., Yang, F., & Cole, G. (1996) · Science · doi:10.1126/science.274.5284.99 · Cited by 4,210
Computed circular dichroism spectra for the evaluation of protein conformation
Greenfield, N. J., & Fasman, G. D. (1969) · Biochemistry · doi:10.1021/bi00838a031 · Cited by 3,697
Bolton, A. E., & Hunter, W. M. (1973) · Biochemical Journal · doi:10.1042/bj1330529 · Cited by 3,240
Immunization with amyloid-β attenuates Alzheimer-disease-like pathology in the PDAPP mouse
Schenk, D., Barbour, R., Dunn, W., Gordon, G., Grajeda, H., Guido, T., Hu, K., Huang, J., Johnson-Wood, K., Khan, K., et al. (1999) · Nature · doi:10.1038/22124 · Cited by 3,160
West, M. J., Slomianka, L., & Gundersen, H. J. G. (1991) · The Anatomical Record · doi:10.1002/ar.1092310411 · Cited by 2,994
GUNDERSEN, H. J. G., BENDTSEN, T. F., KORBO, L., MARCUSSEN, N., MØLLER, A., NIELSEN, K., NYENGAARD, J. R., PAKKENBERG, B., SØRENSEN, F. B., VESTERBY, A., et al. (1988) · APMIS · doi:10.1111/j.1699-0463.1988.tb05320.x · Cited by 2,929
Petkova, A. T., Ishii, Y., Balbach, J. J., Antzutkin, O. N., Leapman, R. D., Delaglio, F., & Tycko, R. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.262663499 · Cited by 1,847
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
Research works printed but not linked: 5
- Stokes A: Humane endpoints in animal experiments for laboratory animals used in toxicity testing. Proceedings of the 3rd World Congress on Alternatives and Animal Use in Life Sciences. 1999 Bologna, Italy
- Kim, 1988, Production and characterization of monoclonal antibodies reactive to synthetic cerebrovascular amyloid peptide, Neurosci Res Commun, 2, 121
- Sadowski, 2001, Effect of the presenilin 1 P117L FAD linked mutation on hippocampal morphology transgenic mice, J Neuropathol Exp Neurol, 60, 543
- Jimenez-Huete, 1998, Antibodies directed to the carboxyl terminus of amyloid β-peptide recognize sequence epitopes and distinct immunoreactive deposits in Alzheimer's disease brain, Alzheimers Rep, 1, 41
- Schenk, 1999, Immunization with amyloid-β attenuates Alzheimer disease-like pathology in the PDAPP mice, Nature, 400, 173, 10.1038/22124 · DOI · Paper page
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Ekuni, D., Endo, Y., Tomofuji, T., Azuma, T., Irie, K., Kasuyama, K., & Morita, M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0074966 · Cited by 16
Boutajangout, A., Goñi, F., Knudsen, E., Schreiber, F., Asuni, A. A., Quartermain, D., Frangione, B., Chabalgoity, A., Wısnıewskı, T., & Sigurdsson, E. M. (2009) · Journal of Alzheimer s Disease · doi:10.3233/jad-2009-1204 · Cited by 15
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Lei, P., Wu, W., Li, R.-W., Ma, J., Yu, Y., Cui, W., Zhao, Y., & Li, Y. (2008) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2008.01.103 · Cited by 14
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Vuletic, S., Li, G., Peskind, E. R., Kennedy, H., Marcovina, S. M., Leverenz, J. B., Petrie, E. C., Lee, V. M.-Y., Galasko, D., Schellenberg, G. D., et al. (2008) · Journal of Alzheimer's Disease · doi:10.3233/jad-2008-15307 · Cited by 12
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Lubecka, E. A., Sikorska, E., Sobolewski, D., Prahl, A., Slaninová, J., & Ciarkowski, J. (2015) · European Biophysics Journal · doi:10.1007/s00249-015-1071-4 · Cited by 9
Malhis, M., & Funke, S. A. (2024) · Current Protocols · doi:10.1002/cpz1.957 · Cited by 8
Camargo, L. C., Gering, I., Mastalipour, M., Kraemer‐Schulien, V., Bujnicki, T., Willbold, D., Coronado, M. A., & Eberle, R. J. (2024) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.4c00089 · Cited by 8
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Martins, I. J., Gupta, V. B., Wilson, A. C., Fuller, S. J., & Martins, R. N. (2014) · Current Proteomics · doi:10.2174/157016461103140922163729 · Cited by 7
Laine, J., Häkkinen, M. R., Auriola, S. O. K., Juvonen, R. O., & Pasanen, M. (2015) · Toxicology Reports · doi:10.1016/j.toxrep.2015.07.002 · Cited by 6
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Xiong, Y., Qu, Y., Min, Z., Wu, J., Zhang, S., & Xue, Z. (2022) · International Journal of Nanomedicine · doi:10.2147/ijn.s351830 · Cited by 4
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Andersson, K. (2005) · KTH Publication Database DiVA (KTH Royal Institute of Technology)
Garzon, D. J., & Mount, J. (2009)
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Chung, J.-Y. (2015) · ERA: Education and Research Archive (University of Alberta) · doi:10.7939/r32h3s
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Metadata
- Authors
- Sadowski, M., Pankiewicz, J., Scholtzova, H., Ripellino, J. A., Li, Y., Schmidt, S. D., Mathews, P. M., Fryer, J. D., Holtzman, D. M., Sigurdsson, E. M., & Wisniewski, T.
- Affiliations
- New York University (US)
- Nathan Kline Institute for Psychiatric Research (US)
- Washington University in St. Louis (US)
- ORCID
- Venue
- The American Journal of Pathology
- Publisher
- Elsevier BV
- Published
- 2004-09
- Volume
- 165
- Issue
- 3
- Pages
- 937-948
- ISSN
- 0002-9440 (ISSN-L)
- PMC
- PMC1618605
- OpenAlex
- W2164642027
- Cited by
- 154
- References
- 87
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 5 · 2023: 4 · 2022: 9 · 2021: 5 · 2020: 7 · 2019: 6 · 2018: 2 · 2017: 1 · 2016: 2 · 2015: 4 · 2014: 9 · 2013: 8 · 2012: 10
- FWCI
- 7.20
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal Of Pathology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (AG15408, AG20747, AG13956)
- 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
- Alzheimer's disease, amyloid-beta, apolipoprotein E, APOE ε4, peptide antagonists, amyloid fibril formation, amyloid plaques, transgenic mice, blood-brain barrier permeability, amyloid deposition
- MeSH terms
- Alzheimer Disease, Animals, Apolipoproteins E, Astrocytes, Binding Sites, Blood-Brain Barrier, Brain, Competitive Bidding, Female, Half-Life, Humans, Male, Membrane Proteins, Mice, Inbred C57BL, Mice, Transgenic, Mutation, Neuroblastoma, Peptide Fragments, Protein Binding, Tumor Cells, Cultured, Amyloid beta-Peptides, Mice, Knockout, Mice, Presenilin-1
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