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Relationship between efficacy and preferential targeting of soluble Aβ aggregates
Kaplan JM, Gibbs E, Coutts JA, Zhao B, Mackenzie IR, Plotkin SS, Cashman NR.. Alzheimer's & dementia (New York, N. Y.), 2025-10-01
Topic: Amyloid, tau and blood-test diagnosis
Introduction Amyloid beta (Aβ)-directed antibodies have shown varying degrees of efficacy against Alzheimer's disease (AD). This study explored the relationship between targeting of Aβ molecular species and therapeutic efficacy/adverse effects. Methods Surface plasmon resonance was used to measure binding of various Aβ-directed antibodies to monomers and soluble oligomers from AD brains. Plaque reactivity was assessed by immunohistochemistry and immunofluorescence. Antibody PMN310 was tested in AD mouse models. Results Pan-Aβ reactive antibodies that failed in the clinic lost the ability to bind AD brain oligomers when competing with monomers. Lecanemab, aducanumab, and donanemab, which slowed cognitive decline, and early stage PMN310 and ACU193 showed a greater ability to withstand monomer competition. All antibodies bound plaque except for PMN310. In mouse models, PMN310 protected cognition and was not associated with microhemorrhages. Discussion These results suggest that selectivity for soluble toxic oligomers correlates with clinical efficacy, potentially attenuating monomer competition and amyloid-related imaging abnormalities (ARIA). Highlights Selectivity for toxic Aβ oligomers has potential to maximize efficacy and safety.Avoidance of Aβ monomers increases binding to toxic AD brain oligomers.Avoidance of Aβ plaque/vascular deposits reduces the risk of ARIA.
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APA 7th
Kaplan, J. M., Gibbs, E., Coutts, J. A., Zhao, B., Mackenzie, I. R., Plotkin, S. S., et al. (2025). Relationship between efficacy and preferential targeting of soluble Aβ aggregates. Alzheimer's & dementia (New York, N. Y.). https://doi.org/10.1002/trc2.70184
Vancouver
Kaplan JM, Gibbs E, Coutts JA, Zhao B, Mackenzie IR, Plotkin SS, et al. Relationship between efficacy and preferential targeting of soluble Aβ aggregates. Alzheimer's & dementia (New York, N. Y.). 2025. doi:10.1002/trc2.70184. PMID: 41323104.
BibTeX
@article{kaplan2025-41323104,
author = {Kaplan, J. M. and Gibbs, E. and Coutts, J. A. and Zhao, B. and Mackenzie, I. R. and Plotkin, S. S. and Cashman, N. R.},
title = {{Relationship between efficacy and preferential targeting of soluble Aβ aggregates}},
journal = {Alzheimer's \& dementia (New York, N. Y.)},
year = {2025},
doi = {10.1002/trc2.70184},
pmid = {41323104},
url = {https://doi.org/10.1002/trc2.70184}
}
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 7 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.
Key findings
- Results Pan-Aβ reactive antibodies that failed in the clinic lost the ability to bind AD brain oligomers when competing with monomers.
- In mouse models, PMN310 protected cognition and was not associated with microhemorrhages.
- Discussion These results suggest that selectivity for soluble toxic oligomers correlates with clinical efficacy, potentially attenuating monomer competition and amyloid-related imaging abnormalities (ARIA).
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Study details
- Evidence strengthLow
How this study scored 48/100
Published in a leading specialty journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 28 of the 58 points we could judge it on, which is 48 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Alzheimer's & dementia (New York, N. Y.)) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41323104) |
| Free to read | 2 / 2 | Free to read |
| Points | 28 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 28 of the 58 points we could judge it on is 48 out of 100. |
| Total | 48 / 100 | — |
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