Bapineuzumab captures the N-terminus of the Alzheimer's disease amyloid-beta peptide in a helical conformation
Open accessAbstract
Bapineuzumab is a humanized antibody developed by Pfizer and Johnson & Johnson targeting the amyloid (Aβ) plaques that underlie Alzheimer's disease neuropathology. Here we report the crystal structure of a Fab-Aβ peptide complex that reveals Bapineuzumab surprisingly captures Aβ in a monomeric helical conformation at the N-terminus. Microscale thermophoresis suggests that the Fab binds soluble Aβ(1-40) with a K(D) of 89 (±9) nM. The structure explains the antibody's exquisite selectivity for particular Aβ species and why it cannot recognize N-terminally modified or truncated Aβ peptides.
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Lecanemab has a normalized rate of amyloid removal of 2.4 CL/4 wk/10mg/kg.
“| Lecanemab | 20 | 62 c /43 | 30 2 | 52 | 2.4 | 10 | 4.2 |”
From The amyloid hypothesis in Alzheimer disease: new insights from new therapeutics (2022) · cites this paper as [114]
Lecanemab removes 62 centiloids in 43 patients.
“| Lecanemab | 20 | 62 c /43 | 30 2 | 52 | 2.4 | 10 | 4.2 |”
From The amyloid hypothesis in Alzheimer disease: new insights from new therapeutics (2022) · cites this paper as [114]
Lecanemab has an ARIA-E/amyloid removal rate index of 4.2.
“| Lecanemab | 20 | 62 c /43 | 30 2 | 52 | 2.4 | 10 | 4.2 |”
From The amyloid hypothesis in Alzheimer disease: new insights from new therapeutics (2022) · cites this paper as [114]
Lecanemab has an incidence of ARIA-E of 10%.
“| Lecanemab | 20 | 62 c /43 | 30 2 | 52 | 2.4 | 10 | 4.2 |”
From The amyloid hypothesis in Alzheimer disease: new insights from new therapeutics (2022) · cites this paper as [114]
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- Authors
- Miles, L. A., Crespi, G. A. N., Doughty, L., & Parker, M. W.
- Affiliations
- Australian Cancer Research Foundation (AU)
- The University of Melbourne (AU)
- Corresponding author
- Parker, Michael W.
- Venue
- Scientific Reports
- Published
- 2013-02-18
- Volume
- 3
- Issue
- 1
- Pages
- 1302-1302
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC3575012
- OpenAlex
- W2033373102
- Cited by
- 130
- References
- 30
- Citations by year
- 2026: 2 · 2025: 9 · 2024: 13 · 2023: 5 · 2022: 6 · 2021: 7 · 2020: 13 · 2019: 11 · 2018: 14 · 2017: 15 · 2016: 7 · 2015: 10 · 2014: 14 · 2013: 4
- FWCI
- 8.10
- Type
- journal article
- Language
- en
- Update notices
- erratum (2013-04-08)
- Open access
- gold
- doi.org
- Licence
- Locations
- Scientific Reports (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by-nc-nd)
- Funders
- Judith Jane Mason and Harold Stannett Williams Memorial Foundation
- Australian Cancer Research Foundation
- Australian Synchrotron
- Medical Research Council
- National Health and Medical Research Council (1021935)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- bapineuzumab, amyloid-beta, Alzheimer's disease, crystal structure, helical conformation, N-terminus, antibody specificity, amyloid plaques, Aβ(1-40), microscale thermophoresis
- MeSH terms
- Alzheimer Disease, Humans, Hydrogen Bonding, Peptide Fragments, Protein Binding, Amyloid beta-Peptides, Protein Structure, Secondary, Crystallography, X-Ray, Antibodies, Monoclonal, Humanized
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