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Novel fully human high-affinity anti-TREM2 antibody shows efficacy in clinically relevant Alzheimer´s mouse model
Markus Kraller, Julia Faßbender, Ammar Jabali, Joseph A. Kroeger, Barbara Fink, Bastian Popper, Martin Ungerer, Miriam A. Christlmeier. Alzheimer s Research & Therapy, 2025-05-22
Topic: Brain proteins, microglia and lab models
M07-TFN showed higher binding affinities and stronger activation of hTREM2 signaling than all previously described anti-hTREM2 antibodies. p-Syk activation was increased 30-fold in hTREM2-overexpressing HEK293 cells and fourfold in human microglia cells compared to baseline. Human microglia viability significantly improved after stress testing. M07-TFN showed strong BBB translocation in a human BBB model, and exerted cross-reactivity to the mouse TREM2 stalk region, which allowed us to investigate M07-TFN directly in an AD mouse model. In 5xFAD mice, M07-TFN resulted in improved novel object location and better spatial orientation and memory, and significantly reduced plaque load. Additional safety investigations in mice showed no negative effects on blood cells or major organs. Compared to existing humanized anti-hTREM2 antibodies that have been investigated in clinical trials, M07-TFN showed best-in-class affinities and agonist potencies. Being a fully human anti-hTREM2 antibody, M07-TFN holds the promise of reduced immunogenicity for use in human patients.
Key findings
- M07-TFN showed higher binding affinities and stronger activation of hTREM2 signaling than all previously described anti-hTREM2 antibodies. p-Syk activation was increased 30-fold in hTREM2-overexpressing HEK293 cells and fourfold in human microglia cells compared to baseline.
- Human microglia viability significantly improved after stress testing.
- M07-TFN showed strong BBB translocation in a human BBB model, and exerted cross-reactivity to the mouse TREM2 stalk region, which allowed us to investigate M07-TFN directly in an AD mouse model.
- In 5xFAD mice, M07-TFN resulted in improved novel object location and better spatial orientation and memory, and significantly reduced plaque load.
- Additional safety investigations in mice showed no negative effects on blood cells or major organs.
Why it matters
This study tested a fully human anti-TREM2 antibody called M07-TFN, which showed strong TREM2 signaling activation, improved human microglia viability, crossed a human blood-brain barrier model, and improved memory and reduced plaque load in 5xFAD mice. These are animal and laboratory results, so it is too early to say whether this antibody treats or prevents Alzheimer's disease in people.
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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 and randomised / blinded because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 36 of the 96 points we could judge it on, which is 38 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Alzheimer s Research & Therapy) |
| Journal's citation record | 1 / 4 | Alzheimer s Research & Therapy: journal h-index 146 (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 | Laboratory or animal study (title names “mouse”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 2 / 7 | Cited 12 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 4.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 3 / 6 | Cited 6.6× 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 | 1 / 4 | Cited 12 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | OpenAlex's profile for last-listed author Miriam A. Christlmeier holds only 2 work(s), too few to judge a track record — left out of this score |
| Institution's track record | 1 / 3 | Ludwig-Maximilians-Universität München: institution h-index 1,224 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40405265) |
| Free to read | 2 / 2 | Free to read |
| Points | 36 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 36 of the 96 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 →
Read the original
- DOI: 10.1186/s13195-025-01759-x
- PubMed: 40405265
- Original source →
- Free full text: Alzheimer s Research & Therapy →
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
Kraller, M., Faßbender, J., Jabali, A., Kroeger, J. A., Fink, B., Popper, B., et al. (2025). Novel fully human high-affinity anti-TREM2 antibody shows efficacy in clinically relevant Alzheimer´s mouse model. Alzheimer s Research & Therapy. https://doi.org/10.1186/s13195-025-01759-x
Vancouver
Kraller M, Faßbender J, Jabali A, Kroeger JA, Fink B, Popper B, et al. Novel fully human high-affinity anti-TREM2 antibody shows efficacy in clinically relevant Alzheimer´s mouse model. Alzheimer s Research & Therapy. 2025. doi:10.1186/s13195-025-01759-x. PMID: 40405265.
BibTeX
@article{kraller2025-40405265,
author = {Kraller, Markus and Faßbender, Julia and Jabali, Ammar and Kroeger, Joseph A. and Fink, Barbara and Popper, Bastian and Ungerer, Martin and Christlmeier, Miriam A.},
title = {{Novel fully human high-affinity anti-TREM2 antibody shows efficacy in clinically relevant Alzheimer´s mouse model}},
journal = {Alzheimer s Research \& Therapy},
year = {2025},
doi = {10.1186/s13195-025-01759-x},
pmid = {40405265},
url = {https://doi.org/10.1186/s13195-025-01759-x}
}
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