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Chronic TREM2 activation exacerbates Aβ-associated tau seeding and spreading
Jain N, Lewis CA, Ulrich JD, Holtzman DM.. The Journal of experimental medicine, 2022-10-11
Topic: Brain proteins, microglia and lab models
Variants in the triggering receptor expressed on myeloid cells 2 (TREM2) gene are associated with increased risk for late-onset AD. Genetic loss of or decreased TREM2 function impairs the microglial response to amyloid-β (Aβ) plaques, resulting in more diffuse Aβ plaques and increased peri-plaque neuritic dystrophy and AD-tau seeding. Thus, microglia and TREM2 are at a critical intersection of Aβ and tau pathologies in AD.
Key findings
- Genetic loss of or decreased TREM2 function impairs the microglial response to amyloid-β (Aβ) plaques, resulting in more diffuse Aβ plaques and increased peri-plaque neuritic dystrophy and AD-tau seeding.
- Thus, microglia and TREM2 are at a critical intersection of Aβ and tau pathologies in AD.
- Since genetically decreasing TREM2 function increases Aβ-induced tau seeding, we hypothesized that chronically increasing TREM2 signaling would decrease amyloid-induced tau-seeding and spreading.
- Using a mouse model of amyloidosis in which AD-tau is injected into the brain to induce Aβ-dependent tau seeding/spreading, we found that chronic administration of an activating TREM2 antibody increases peri-plaque microglial activation but surprisingly increases peri-plaque NP-tau pathology and neuritic dystrophy, without altering Aβ plaque burden.
Why it matters
In mice, chronically increasing TREM2 signaling worsened amyloid-associated tau seeding and spreading, contrary to the researchers' hypothesis. This is animal research showing a harmful effect of one approach, not a treatment.
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Study details
- Evidence strengthLow
How this study scored 55/100
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.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The Journal of experimental medicine) |
| Journal's citation record | 4 / 4 | The Journal of Experimental Medicine: journal h-index 652 (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 143 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 28.6 citations a year over 5 year(s) since 2023 |
| Impact for its field and year | 4 / 6 | Cited 14.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 18 other studies in this library |
| Still being cited | 3 / 4 | Cited 108 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 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 36219197) |
| Free to read | 2 / 2 | Free to read |
| Total | 55 / 100 | — |
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Read the original
- DOI: 10.1084/jem.20220654
- PubMed: 36219197
- Original source →
- Free full text: The Journal of Experimental Medicine →
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. Check the citation against the original before you use it.
APA 7th
Jain, N., Lewis, C. A., Ulrich, J. D., & Holtzman, D. M. (2023). Chronic TREM2 activation exacerbates Aβ-associated tau seeding and spreading. The Journal of experimental medicine. https://doi.org/10.1084/jem.20220654
Vancouver
Jain N, Lewis CA, Ulrich JD, Holtzman DM. Chronic TREM2 activation exacerbates Aβ-associated tau seeding and spreading. The Journal of experimental medicine. 2023. doi:10.1084/jem.20220654. PMID: 36219197.
BibTeX
@article{jain2023-36219197,
author = {Jain, N. and Lewis, C. A. and Ulrich, J. D. and Holtzman, D. M.},
title = {{Chronic TREM2 activation exacerbates Aβ-associated tau seeding and spreading}},
journal = {The Journal of experimental medicine},
year = {2023},
doi = {10.1084/jem.20220654},
pmid = {36219197},
url = {https://doi.org/10.1084/jem.20220654}
}
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