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Plaque contact and unimpaired Trem2 is required for the microglial response to amyloid pathology
Wood JI, Wong E, Joghee R, Balbaa A, Vitanova KS, Stringer KM, Vanshoiack A, Phelan SJ et al.. Cell reports, 2022-11-01
Topic: Brain proteins, microglia and lab models
Using spatial cell-type-enriched transcriptomics, we compare plaque-induced gene (PIG) expression in microglia-touching plaques, neighboring plaques, and far from plaques in an aged Alzheimer's mouse model with late plaque development. In 18-month-old APP NL-F/NL-F knockin mice, with and without the Alzheimer's disease risk mutation Trem2 R47H/R47H , we report that expression of 38/55 PIGs have plaque-induced microglial upregulation, with a subset only upregulating in microglia directly contacting plaques. For seven PIGs, including Trem2, this upregulation is prevented in APP NL-F/NL-F Trem2 R47H/R47H mice.
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APA 7th
Wood, J. I., Wong, E., Joghee, R., Balbaa, A., Vitanova, K. S., Stringer, K. M., et al. (2022). Plaque contact and unimpaired Trem2 is required for the microglial response to amyloid pathology. Cell reports. https://doi.org/10.1016/j.celrep.2022.111686
Vancouver
Wood JI, Wong E, Joghee R, Balbaa A, Vitanova KS, Stringer KM, et al. Plaque contact and unimpaired Trem2 is required for the microglial response to amyloid pathology. Cell reports. 2022. doi:10.1016/j.celrep.2022.111686. PMID: 36417868.
BibTeX
@article{wood2022-36417868,
author = {Wood, J. I. and Wong, E. and Joghee, R. and Balbaa, A. and Vitanova, K. S. and Stringer, K. M. and Vanshoiack, A. and Phelan, S. J. and others},
title = {{Plaque contact and unimpaired Trem2 is required for the microglial response to amyloid pathology}},
journal = {Cell reports},
year = {2022},
doi = {10.1016/j.celrep.2022.111686},
pmid = {36417868},
url = {https://doi.org/10.1016/j.celrep.2022.111686}
}
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Key findings
- In 18-month-old APP NL-F/NL-F knockin mice, with and without the Alzheimer's disease risk mutation Trem2 R47H/R47H , we report that expression of 38/55 PIGs have plaque-induced microglial upregulation, with a subset only upregulating in microglia directly contacting plaques.
- For seven PIGs, including Trem2, this upregulation is prevented in APP NL-F/NL-F Trem2 R47H/R47H mice.
- These TREM2-dependent genes are all involved in phagocytic and degradative processes that we show correspond to a decrease in phagocytic markers and an increase in the density of small plaques in Trem2-mutated mice.
- Furthermore, despite the R47H mutation preventing increased Trem2 gene expression, TREM2 protein levels and microglial density are still marginally increased on plaques.
Why it matters
In aged Alzheimer's mouse models, this study found that plaque-induced gene upregulation in microglia, including for TREM2, is prevented by the Trem2 R47H/R47H risk mutation, and that TREM2-dependent genes relate to phagocytic and degradative processes. These are animal findings about microglial response to amyloid plaques and do not demonstrate a treatment or cure.
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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, studied in people and randomized / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Cell reports) |
| Journal's citation record | 3 / 4 | Cell Reports: journal h-index 321 (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 | 2022 — 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) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 4 / 7 | Cited 59 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 9.8 citations a year over 6 year(s) since 2022 |
| Impact for its field and year | 3 / 6 | Cited 3.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 4 other studies in this library |
| Still being cited | 3 / 4 | Cited 51 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Frances A. Edwards: h-index 29 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University College London: institution h-index 2,029 (OpenAlex) |
| Multicenter collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 36417868) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 47 / 100 | — |
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