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A TREM2-activating antibody with a blood-brain barrier transport vehicle enhances microglial metabolism in Alzheimer's disease models
van Lengerich B, Zhan L, Xia D, Chan D, Joy D, Park JI, Tatarakis D, Calvert M et al.. Nature neuroscience, 2023-01-12
Topic: Brain proteins, microglia and lab models
Loss-of-function variants of TREM2 are associated with increased risk of Alzheimer's disease (AD), suggesting that activation of this innate immune receptor may be a useful therapeutic strategy. Here we describe a high-affinity human TREM2-activating antibody engineered with a monovalent transferrin receptor (TfR) binding site, termed antibody transport vehicle (ATV), to facilitate blood-brain barrier transcytosis. Upon peripheral delivery in mice, ATV:TREM2 showed improved brain biodistribution and enhanced signaling compared to a standard anti-TREM2 antibody.
Key findings
- Here we describe a high-affinity human TREM2-activating antibody engineered with a monovalent transferrin receptor (TfR) binding site, termed antibody transport vehicle (ATV), to facilitate blood-brain barrier transcytosis.
- Upon peripheral delivery in mice, ATV:TREM2 showed improved brain biodistribution and enhanced signaling compared to a standard anti-TREM2 antibody.
- In human induced pluripotent stem cell (iPSC)-derived microglia, ATV:TREM2 induced proliferation and improved mitochondrial metabolism.
- Single-cell RNA sequencing and morphometry revealed that ATV:TREM2 shifted microglia to metabolically responsive states, which were distinct from those induced by amyloid pathology.
Why it matters
Researchers built a TREM2-activating antibody designed to cross the blood-brain barrier and tested it in mice and in human cells grown in the lab. This is early experimental work and does not show any benefit for treating Alzheimer's disease in people.
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Study details
- Evidence strengthLow
How this study scored 55/100
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.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Nature neuroscience) |
| Journal's citation record | 4 / 4 | Nature Neuroscience: journal h-index 593 (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 | 3 / 5 | 2023 — within 6 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 | 5 / 7 | Cited 226 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 45.2 citations a year over 5 year(s) since 2023 |
| Impact for its field and year | 4 / 6 | Cited 18.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 15 other studies in this library |
| Still being cited | 3 / 4 | Cited 189 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Kathryn M. Monroe: h-index 21 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Ludwig-Maximilians-Universität München: institution h-index 1,224 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 36635496) |
| Free to read | 2 / 2 | Free to read |
| Total | 55 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1038/s41593-022-01240-0
- PubMed: 36635496
- Original source →
- Free full text: Nature Neuroscience →
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'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
van Lengerich, B., Zhan, L., Xia, D., Chan, D., Joy, D., Park, J. I., et al. (2023). A TREM2-activating antibody with a blood-brain barrier transport vehicle enhances microglial metabolism in Alzheimer's disease models. Nature neuroscience. https://doi.org/10.1038/s41593-022-01240-0
Vancouver
van Lengerich B, Zhan L, Xia D, Chan D, Joy D, Park JI, et al. A TREM2-activating antibody with a blood-brain barrier transport vehicle enhances microglial metabolism in Alzheimer's disease models. Nature neuroscience. 2023. doi:10.1038/s41593-022-01240-0. PMID: 36635496.
BibTeX
@article{vanlengerich2023-36635496,
author = {van Lengerich, B. and Zhan, L. and Xia, D. and Chan, D. and Joy, D. and Park, J. I. and Tatarakis, D. and Calvert, M. and others},
title = {{A TREM2-activating antibody with a blood-brain barrier transport vehicle enhances microglial metabolism in Alzheimer's disease models}},
journal = {Nature neuroscience},
year = {2023},
doi = {10.1038/s41593-022-01240-0},
pmid = {36635496},
url = {https://doi.org/10.1038/s41593-022-01240-0}
}
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