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Acute Trem2 reduction triggers increased microglial phagocytosis, slowing amyloid deposition in mice
Schoch KM, Ezerskiy LA, Morhaus MM, Bannon RN, Sauerbeck AD, Shabsovich M, Jafar-Nejad P, Rigo F et al.. Proceedings of the National Academy of Sciences of the United States of America, 2021-07-01
Topic: Brain proteins, microglia and lab models
Heterozygous genetic variants within the TREM2 gene show a strong association with increased Alzheimer's disease (AD) risk. Amyloid beta-depositing mouse models haploinsufficient or null for Trem2 have identified important relationships among TREM2, microglia, and AD pathology; however, results are challenging to interpret in the context of varying microglial phenotypes and disease progression. We hypothesized that acute Trem2 reduction may alter amyloid pathology and microglial responses independent of genetic Trem2 deletion in mouse models.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Schoch, K. M., Ezerskiy, L. A., Morhaus, M. M., Bannon, R. N., Sauerbeck, A. D., Shabsovich, M., et al. (2021). Acute Trem2 reduction triggers increased microglial phagocytosis, slowing amyloid deposition in mice. Proceedings of the National Academy of Sciences of the United States of America. https://doi.org/10.1073/pnas.2100356118
Vancouver
Schoch KM, Ezerskiy LA, Morhaus MM, Bannon RN, Sauerbeck AD, Shabsovich M, et al. Acute Trem2 reduction triggers increased microglial phagocytosis, slowing amyloid deposition in mice. Proceedings of the National Academy of Sciences of the United States of America. 2021. doi:10.1073/pnas.2100356118. PMID: 34187891.
BibTeX
@article{schoch2021-34187891,
author = {Schoch, K. M. and Ezerskiy, L. A. and Morhaus, M. M. and Bannon, R. N. and Sauerbeck, A. D. and Shabsovich, M. and Jafar-Nejad, P. and Rigo, F. and others},
title = {{Acute Trem2 reduction triggers increased microglial phagocytosis, slowing amyloid deposition in mice}},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {2021},
doi = {10.1073/pnas.2100356118},
pmid = {34187891},
url = {https://doi.org/10.1073/pnas.2100356118}
}
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Key findings
- Amyloid beta-depositing mouse models haploinsufficient or null for Trem2 have identified important relationships among TREM2, microglia, and AD pathology; however, results are challenging to interpret in the context of varying microglial phenotypes and disease progression.
- We hypothesized that acute Trem2 reduction may alter amyloid pathology and microglial responses independent of genetic Trem2 deletion in mouse models.
- We developed antisense oligonucleotides (ASOs) that potently but transiently lower Trem2 messenger RNA throughout the brain and administered them to APP/PS1 mice at varying stages of plaque pathology.
- Late-stage ASO-mediated Trem2 knockdown significantly reduced plaque deposition and attenuated microglial association around plaque deposits when evaluated 1 mo after ASO injection.
Why it matters
In mice, acutely reducing Trem2 with antisense oligonucleotides increased microglial phagocytosis and slowed amyloid deposition. This is an early animal study and does not yet show a treatment, cure, or prevention for Alzheimer's disease in people.
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Study details
- Evidence strengthLow
How this study scored 47/100
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.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Proceedings of the National Academy of Sciences of the United States of America) |
| Journal's citation record | 4 / 4 | Proceedings of the National Academy of Sciences: journal h-index 1,167 (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 | 2021 — 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 | Laboratory or animal study (title names “mice”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 4 / 7 | Cited 76 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 10.9 citations a year over 7 year(s) since 2021 |
| Impact for its field and year | 3 / 6 | Cited 4.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 8 other studies in this library |
| Still being cited | 2 / 4 | Cited 39 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Timothy M. Miller: h-index 60 (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 34187891) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 47 / 100 | — |
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