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Kinetic fingerprints differentiate the mechanisms of action of anti-Aβ antibodies
Linse S, Scheidt T, Bernfur K, Vendruscolo M, Dobson CM, Cohen SIA, Sileikis E, Lundqvist M et al.. Nature structural & molecular biology, 2020-09-28
Topic: Disease mechanisms in lab and animal studies
The amyloid cascade hypothesis, according to which the self-assembly of amyloid-β peptide (Aβ) is a causative process in Alzheimer's disease, has driven many therapeutic efforts for the past 20 years. Failures of clinical trials investigating Aβ-targeted therapies have been interpreted as evidence against this hypothesis, irrespective of the characteristics and mechanisms of action of the therapeutic agents, which are highly challenging to assess. Here, we combine kinetic analyses with quantitative binding measurements to address the mechanism of action of four clinical stage anti-Aβ antibodies, aducanumab, gantenerumab, bapineuzumab and solanezumab. We quantify the influence of these antibodies on the aggregation kinetics and on the production of oligomeric aggregates and link these effects to the affinity and stoichiometry of each antibody for monomeric and fibrillar forms of Aβ. Our results reveal that, uniquely among these four antibodies, aducanumab dramatically reduces the flux of Aβ oligomers.
Key findings
- Our results reveal that, uniquely among these four antibodies, aducanumab dramatically reduces the flux of Aβ oligomers.
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Study details
- Evidence strengthLow
How this study scored 38/100
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. 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 22 of the 58 points we could judge it on, which is 38 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Nature structural & molecular biology) |
| 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 | 2 / 5 | 2020 — within 10 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 32989305) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 22 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 22 of the 58 points we could judge it on is 38 out of 100. |
| Total | 38 / 100 | — |
What each of these 20 components measures, and what this score is not →
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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's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Linse, S., Scheidt, T., Bernfur, K., Vendruscolo, M., Dobson, C. M., Cohen, S. I. A., et al. (2020). Kinetic fingerprints differentiate the mechanisms of action of anti-Aβ antibodies. Nature structural & molecular biology. https://doi.org/10.1038/s41594-020-0505-6
Vancouver
Linse S, Scheidt T, Bernfur K, Vendruscolo M, Dobson CM, Cohen SIA, et al. Kinetic fingerprints differentiate the mechanisms of action of anti-Aβ antibodies. Nature structural & molecular biology. 2020. doi:10.1038/s41594-020-0505-6. PMID: 32989305.
BibTeX
@article{linse2020-32989305,
author = {Linse, S. and Scheidt, T. and Bernfur, K. and Vendruscolo, M. and Dobson, C. M. and Cohen, S. I. A. and Sileikis, E. and Lundqvist, M. and others},
title = {{Kinetic fingerprints differentiate the mechanisms of action of anti-Aβ antibodies}},
journal = {Nature structural \& molecular biology},
year = {2020},
doi = {10.1038/s41594-020-0505-6},
pmid = {32989305},
url = {https://doi.org/10.1038/s41594-020-0505-6}
}
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