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TREM2 function impedes tau seeding in neuritic plaques
Leyns CEG, Gratuze M, Narasimhan S, Jain N, Koscal LJ, Jiang H, Manis M, Colonna M et al.. Nature neuroscience, 2019-06-24
Topic: Brain proteins, microglia and lab models
Variants in the triggering receptor expressed on myeloid cells 2 (TREM2) have been associated with increased risk for sporadic, late-onset Alzheimer's disease. Here we show that germline knockout of Trem2 or the TREM2 R47H variant reduces microgliosis around amyloid-β plaques and facilitates the seeding and spreading of neuritic plaque tau aggregates. These findings demonstrate a key role for TREM2 and microglia in limiting the development of peri-plaque tau pathologies.
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APA 7th
Leyns, C. E. G., Gratuze, M., Narasimhan, S., Jain, N., Koscal, L. J., Jiang, H., et al. (2019). TREM2 function impedes tau seeding in neuritic plaques. Nature neuroscience. https://doi.org/10.1038/s41593-019-0433-0
Vancouver
Leyns CEG, Gratuze M, Narasimhan S, Jain N, Koscal LJ, Jiang H, et al. TREM2 function impedes tau seeding in neuritic plaques. Nature neuroscience. 2019. doi:10.1038/s41593-019-0433-0. PMID: 31235932.
BibTeX
@article{leyns2019-31235932,
author = {Leyns, C. E. G. and Gratuze, M. and Narasimhan, S. and Jain, N. and Koscal, L. J. and Jiang, H. and Manis, M. and Colonna, M. and others},
title = {{TREM2 function impedes tau seeding in neuritic plaques}},
journal = {Nature neuroscience},
year = {2019},
doi = {10.1038/s41593-019-0433-0},
pmid = {31235932},
url = {https://doi.org/10.1038/s41593-019-0433-0}
}
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Key findings
- Here we show that germline knockout of Trem2 or the TREM2 R47H variant reduces microgliosis around amyloid-β plaques and facilitates the seeding and spreading of neuritic plaque tau aggregates.
- These findings demonstrate a key role for TREM2 and microglia in limiting the development of peri-plaque tau pathologies.
Why it matters
In mice, removing Trem2 or carrying the R47H variant reduced microglia around amyloid plaques and allowed neuritic plaque tau aggregates to seed and spread more easily. This shows TREM2 and microglia help limit tau pathology near plaques, but it is animal work.
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Study details
- Evidence strengthLow
How this study scored 59/100
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 | 2 / 5 | 2019 — 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 | 6 / 7 | Cited 333 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 37.0 citations a year over 9 year(s) since 2019 |
| Impact for its field and year | 5 / 6 | Cited 22.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 53 other studies in this library |
| Still being cited | 3 / 4 | Cited 125 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author David M. Holtzman: h-index 206 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Washington University in St. Louis: institution h-index 1,962 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 31235932) |
| Free to read | 2 / 2 | Free to read |
| Total | 59 / 100 | — |
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