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Inhibition of tau neuronal internalization using anti-tau single domain antibodies
Clément Danis, Elian Dupré, Thomas Bouillet, Marine Denéchaud, Camille Lefebvre, Marine Nguyen, Justine Mortelecque, François-Xavier Cantrelle et al.. Nature communications, 2025-04-02
Topic: Disease mechanisms in lab and animal studies
In Alzheimer's disease, tau pathology spreads across brain regions as the disease progresses. Intracellular tau can be released and taken up by nearby neurons. We evaluated single domain anti-tau antibodies, also called VHHs, as inhibitors of tau internalization. We identified three VHH inhibitors of tau uptake: A31, H3-2, and Z70mut1. These VHHs compete with the membrane protein LRP1, a major receptor mediating neuronal uptake of tau. A31 and Z70mut1 bind to microtubule binding domain repeats, which are involved in the interaction with LRP1. VHH H3-2 is the only VHH from our library that reduces the internalization of both monomeric tau and tau fibrils. VHH H3-2 binds a C-terminal tau epitope with high affinity. Its three-dimensional structure in complex with a tau peptide reveals a unique binding mode as a VHH-swapped dimer. These anti-tau VHHs are interesting tools to study tau prion-like propagation in tauopathies and potentially develop novel biotherapies.
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APA 7th
Danis, C., Dupré, E., Bouillet, T., Denéchaud, M., Lefebvre, C., Nguyen, M., et al. (2025). Inhibition of tau neuronal internalization using anti-tau single domain antibodies. Nature communications. https://doi.org/10.1038/s41467-025-58383-4
Vancouver
Danis C, Dupré E, Bouillet T, Denéchaud M, Lefebvre C, Nguyen M, et al. Inhibition of tau neuronal internalization using anti-tau single domain antibodies. Nature communications. 2025. doi:10.1038/s41467-025-58383-4. PMID: 40175345.
BibTeX
@article{danis2025-40175345,
author = {Danis, Clément and Dupré, Elian and Bouillet, Thomas and Denéchaud, Marine and Lefebvre, Camille and Nguyen, Marine and Mortelecque, Justine and Cantrelle, François-Xavier and others},
title = {{Inhibition of tau neuronal internalization using anti-tau single domain antibodies}},
journal = {Nature communications},
year = {2025},
doi = {10.1038/s41467-025-58383-4},
pmid = {40175345},
url = {https://doi.org/10.1038/s41467-025-58383-4}
}
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Key findings
- A31 and Z70mut1 bind to microtubule binding domain repeats, which are involved in the interaction with LRP1.
- VHH H3-2 is the only VHH from our library that reduces the internalization of both monomeric tau and tau fibrils.
- VHH H3-2 binds a C-terminal tau epitope with high affinity.
- Its three-dimensional structure in complex with a tau peptide reveals a unique binding mode as a VHH-swapped dimer.
- These anti-tau VHHs are interesting tools to study tau prion-like propagation in tauopathies and potentially develop novel biotherapies.
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Study details
- Evidence strengthLow
How this study scored 46/100
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, multi-centre collaboration and free to read, so those were left out: it earned 26 of the 56 points we could judge it on, which is 46 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Nature communications) |
| 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 40175345) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 26 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 26 of the 56 points we could judge it on is 46 out of 100. |
| Total | 46 / 100 | — |
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