Epitomic Characterization of the Specificity of the Anti-Amyloid Aβ Monoclonal Antibodies 6E10 and 4G8
Open accessAbstract
The monoclonal antibodies 6E10 and 4G8 are among the first anti-amyloid monoclonal antibodies against Aβ and the most widely used antibodies in Alzheimer's disease research. Although the epitopes for 6E10 and 4G8 have been reported to correspond to residues 1-16 and 17-24, a more recent high-resolution mapping approach indicates that 6E10 maps to residues 4-10 while 4G8 maps to residues 18-23. To characterize the binding specificity of both antibodies in greater detail, we used immunoselection of random sequences from phage display library followed by deep sequencing and analysis of resulting patterns from thousands of immunoselected sequences. We found that the minimum sequence required for 6E10 binding is R-x-D with over half (53%) of the immunoselected sequences conforming to this pattern. The vast majority of these sequences contain an H at position x (R-H-D), corresponding to residues 5-7 of the Aβ target sequences, but Y is also permitted at this position in a minority of sequences. For 4G8 we found that the most frequent pattern is F-x-A contained in approximately 30% of the sequences, followed by F-A, L-x(3)-A, L-x-F, and F-F each accounting for approximately 18% of the sequences. The F-x-A motif also occurs in islet amyloid poly peptide which may explain why 4G8 also recognizes amyloid fibrils of this peptide. Immunoselection of random sequences and deep sequencing may also be a facile and efficient means of determining residues critical for antibody binding and validating the specificity of monoclonal antibodies and polyclonal antisera.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The assay detects at least dimers because it requires binding of two copies of the same antibody 6E10, which has a single epitope.
“It relies on the binding of 2 copies of the same antibody (6E10, which only has a single epitope [66]), ensuring that what are detected are at least dimers.”
From Selective suppression of oligodendrocyte-derived amyloid beta rescues neuronal dysfunction in Alzheimer’s disease (2024) · cites this paper as [66]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease
Sevigny, J., Chiao, P., Bussière, T., Weinreb, P. H., Williams, L., Maier, M., Dunstan, R., Salloway, S., Chen, T., Ling, Y., et al. (2016) · Nature · doi:10.1038/nature19323 · Cited by 3,059 · see citing works
Neuropathology of human Alzheimer disease after immunization with amyloid-β peptide: a case report
Nicoll, J. A. R., Wilkinson, D., Holmes, C., Steart, P., Markham, H., & Weller, R. O. (2003) · Nature Medicine · doi:10.1038/nm840 · Cited by 1,397 · see citing works
Purification of Nucleic Acids by Extraction with Phenol:Chloroform
Sambrook, J., & Russell, D. W. (2006) · Cold Spring Harbor Protocols · doi:10.1101/pdb.prot4455 · Cited by 1,047 · see citing works
Random Peptide Libraries: a Source of Specific Protein Binding Molecules
Devlin, J. J., Panganiban, L. C., & Devlin, P. E. (1990) · Science · doi:10.1126/science.2143033 · Cited by 923 · see citing works
Structural Classification of Toxic Amyloid Oligomers
Glabe, C. G. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.r800016200 · Cited by 783 · see citing works
Self-citationFelici, F., Castagnoli, L., Musacchio, A., Jappelli, R., & Cesareni, G. (1991) · Journal of Molecular Biology · doi:10.1016/0022-2836(91)90213-p · Cited by 395 · see citing works
Finding flexible patterns in unaligned protein sequences
Jonassen, I., Collins, J., & Higgins, D. G. (1995) · Protein Science · doi:10.1002/pro.5560040817 · Cited by 297 · see citing works
Immunotherapeutic Approaches for Alzheimer’s Disease
Wisniewski, T., & Goñi, F. (2015) · Neuron · doi:10.1016/j.neuron.2014.12.064 · Cited by 284 · see citing works
Kayed, R., Canto, I., Breydo, L., Rasool, S., Lukácsovich, T., Wu, J., Albay, R., Pensalfini, A., Yeung, S. T., Head, E., et al. (2010) · Molecular Neurodegeneration · doi:10.1186/1750-1326-5-57 · Cited by 155 · see citing works
Self-citationEfficient discovery of conserved patterns using a pattern graph
Jonassen, I. (1997) · Computer applications in the biosciences · doi:10.1093/bioinformatics/13.5.509 · Cited by 151 · see citing works
Hatami, A., Albay, R., Monjazeb, S., Milton, S. C. F., & Glabe, C. G. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.594846 · Cited by 121 · see citing works
Self-citationRygiel, K. (2016) · Indian Journal of Pharmacology · doi:10.4103/0253-7613.194867 · Cited by 74 · see citing works
Hatami, A., Monjazeb, S., & Glabe, C. G. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-150696 · Cited by 31 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Rajani, R. M., Ellingford, R., Hellmuth, M., Harris, S. S., Taso, O. S., Graykowski, D., Lam, F. K. W., Arber, C., Fertan, E., Danial, J. S. H., et al. (2024) · PLOS Biology · doi:10.1371/journal.pbio.3002727 · Cited by 57 · see citing works
Serum amyloid P secreted by bone marrow adipocytes drives skeletal amyloidosis
Kumar, S., Song, K., Wang, J., Baghel, M. S., Zeng, Y., Shen, K., Zheng, J., Crane, J., Demehri, S., Gao, P., et al. (2025) · Nature Aging · doi:10.1038/s43587-025-00924-z · Cited by 16 · see citing works
Bevan, R. J., Maguire, E., Mackinnon, E., Salis, E., Phillips, T., Simonazzi, E., Vassileva, M., Allen, N. D., Williams, J., & Taylor, P. R. (2026) · Glia · doi:10.1002/glia.70192 · Cited by 1 · see citing works
- Authors
- Baghallab, I., Reyes-Ruiz, J. M., Abulnaja, K., Huwait, E., & Glabe, C.
- Affiliations
- King Abdulaziz University (SA)
- Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA, USA
- University of California, Irvine (US)
- Corresponding author
- Glabe, Charles
- Venue
- Journal of Alzheimer s Disease
- Publisher
- SAGE Publications
- Published
- 2018-11-05
- Volume
- 66
- Issue
- 3
- Pages
- 1235-1244
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- PMC
- PMC6294585
- OpenAlex
- W2899520465
- Cited by
- 95
- References
- 13
- Citations by year
- 2026: 20 · 2025: 12 · 2024: 21 · 2023: 11 · 2022: 11 · 2021: 6 · 2020: 12 · 2019: 2
- FWCI
- 3.43
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Alzheimer s Disease (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc)
- Funders
- Cure Alzheimer's Fund
- King Abdulaziz University
- University of California, Irvine
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- anti-amyloid monoclonal antibodies
- MeSH terms
- Amyloid, Antibodies, Monoclonal, Epitopes, Humans, Amyloid beta-Peptides, Epitope Mapping
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
