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Lecanemab, aducanumab, and donanemab bind the same human Alzheimer disease Aβ aggregates at different epitopes
Andrew M. Stern, Anna G. Francis, Angela L. Meunier, Amirah K. Anderson, Elizabeth L. Hennessey, Michael B. Miller, Cynthia Ann Lemere, Dennis J. Selkoe. Alzheimer s & Dementia, 2025-12-01
Topic: Amyloid, tau and blood-test diagnosis
Abstract Background Lecanemab, donanemab, and aducanumab all bind to aggregates of Aβ and all clear amyloid PET in clinical trials, but they are proposed to bind different forms of Aβ and cause amyloid related imaging abnormality (ARIA) at different rates. We tested the binding properties of in‐house recombinant versions of these antibodies to soluble (aqueous), detergent‐insoluble, amyloid plaque‐enriched, and cerebral amyloid angiopathy (CAA)‐enriched extracts of human AD brain. Methods We developed a new immunoprecipitation‐ELISA method for measuring antibody equilibrium binding affinity (K D ) and total antigen availability (B max ) to Aβ40‐rich aggregates from leptomeninges, likely principally CAA, and to Aβ42‐rich aggregates from grey matter, likely principally plaque, in aqueous and N ‐lauryl‐sarcosine‐insoluble fractions. We used linear mixed models to measure differences and correlations between antibody K D , B max , and ratios thereof, and the effects of APOE genotype and sex across 18 AD cases. Results The B max was highly correlated between antibodies ( r > 0.9) for all Aβ aggregate extracts. Lecanemab did not exhibit a preference for aqueous Aβ (“protofibrils”) compared to aducanumab. Aducanumab, which causes the most ARIA, did not consistently exhibit greater preference for CAA Aβ compared to lecanemab or donanemab, which cause less ARIA. Conclusions Within the limitations of measuring in vitro equilibrium binding activity of in‐house recombinant antibodies to aqueously extracted Aβ from human postmortem brain tissue, we could not discern a population of Aβ aggregates ( e.g . protofibrils) accessible to one antibody but not the other two. Antibody preference for CAA Aβ over plaque Aβ does not explain differences in clinical trial ARIA rates.
Key findings
- Results The B max was highly correlated between antibodies ( r > 0.9) for all Aβ aggregate extracts.
- Lecanemab did not exhibit a preference for aqueous Aβ (“protofibrils”) compared to aducanumab.
- Aducanumab, which causes the most ARIA, did not consistently exhibit greater preference for CAA Aβ compared to lecanemab or donanemab, which cause less ARIA.
Why it matters
This laboratory study found that lecanemab, aducanumab, and donanemab bind the same human Alzheimer's Aβ aggregates at different sites, and that lecanemab did not prefer soluble Aβ over aducanumab. It also found that aducanumab, which causes the most ARIA, did not consistently prefer cerebral amyloid angiopathy Aβ, so it does not explain why these antibodies cause ARIA at different rates.
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Study details
- Evidence strengthLow
How this study scored 36/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Alzheimer s & Dementia) |
| Journal's citation record | 2 / 4 | Alzheimer s & Dementia: journal h-index 228 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 0 / 7 | Cited 0 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 0 / 6 | Cited 0.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 0 / 4 | Cited 0 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Dennis J. Selkoe: h-index 174 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41435407) |
| Free to read | 2 / 2 | Free to read |
| Total | 36 / 100 | — |
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Read the original
- DOI: 10.1002/alz70855_099914
- PubMed: 41435407
- Original source →
- Free full text: Alzheimer s & Dementia →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Stern, A. M., Francis, A. G., Meunier, A. L., Anderson, A. K., Hennessey, E. L., Miller, M. B., et al. (2025). Lecanemab, aducanumab, and donanemab bind the same human Alzheimer disease Aβ aggregates at different epitopes. Alzheimer s & Dementia. https://doi.org/10.1002/alz70855_099914
Vancouver
Stern AM, Francis AG, Meunier AL, Anderson AK, Hennessey EL, Miller MB, et al. Lecanemab, aducanumab, and donanemab bind the same human Alzheimer disease Aβ aggregates at different epitopes. Alzheimer s & Dementia. 2025. doi:10.1002/alz70855_099914. PMID: 41435407.
BibTeX
@article{stern2025-41435407,
author = {Stern, Andrew M. and Francis, Anna G. and Meunier, Angela L. and Anderson, Amirah K. and Hennessey, Elizabeth L. and Miller, Michael B. and Lemere, Cynthia Ann and Selkoe, Dennis J.},
title = {{Lecanemab, aducanumab, and donanemab bind the same human Alzheimer disease Aβ aggregates at different epitopes}},
journal = {Alzheimer s \& Dementia},
year = {2025},
doi = {10.1002/alz70855_099914},
pmid = {41435407},
url = {https://doi.org/10.1002/alz70855_099914}
}
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