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The TREM2 H157Y Variant Influences Microglial Phagocytosis, Polarization, and Inflammatory Cytokine Release
Xin-Xin Fu, Shuai-Yu Chen, Hui-Wen Lian, Yang Deng, Rui Duan, Ying-Dong Zhang, Teng Jiang. Brain sciences, 2023-04-09
Topic: Inflammation, microglia and astrocytes
Previously, we reported that H157Y, a rare coding variant on exon 3 of the triggering receptor expressed on myeloid cells 2 gene (TREM2), was associated with Alzheimer's disease (AD) risk in a Han Chinese population. To date, how this variant increases AD risk has remained unclear. In this study, using CRISPR-Cas9-engineered BV2 microglia, we tried to investigate the influence of the Trem2 H157Y variant on AD-related microglial functions. For the first time, we revealed that the Trem2 H157Y variant inhibits microglial phagocytosis of amyloid-β, promotes M1-type polarization of microglia, and facilitates microglial release of inflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α. These findings provide new insights into the cellular mechanisms by which the TREM2 H157Y variant elevates the risk of AD.
Key findings
- Previously, we reported that H157Y, a rare coding variant on exon 3 of the triggering receptor expressed on myeloid cells 2 gene (TREM2), was associated with Alzheimer's disease (AD) risk in a Han Chinese population.
- For the first time, we revealed that the Trem2 H157Y variant inhibits microglial phagocytosis of amyloid-β, promotes M1-type polarization of microglia, and facilitates microglial release of inflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α.
- These findings provide new insights into the cellular mechanisms by which the TREM2 H157Y variant elevates the risk of AD.
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Study details
- Evidence strengthLow
How this study scored 41/100
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. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record, multi-centre collaboration and free to read, so those were left out: it earned 23 of the 56 points we could judge it on, which is 41 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Brain sciences) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 37190607) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 23 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 23 of the 56 points we could judge it on is 41 out of 100. |
| Total | 41 / 100 | — |
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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 names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Fu, X.-X., Chen, S.-Y., Lian, H.-W., Deng, Y., Duan, R., Zhang, Y.-D., et al. (2023). The TREM2 H157Y Variant Influences Microglial Phagocytosis, Polarization, and Inflammatory Cytokine Release. Brain sciences. https://doi.org/10.3390/brainsci13040642
Vancouver
Fu X.-X, Chen S.-Y, Lian H.-W, Deng Y, Duan R, Zhang Y.-D, et al. The TREM2 H157Y Variant Influences Microglial Phagocytosis, Polarization, and Inflammatory Cytokine Release. Brain sciences. 2023. doi:10.3390/brainsci13040642. PMID: 37190607.
BibTeX
@article{fu2023-37190607,
author = {Fu, Xin-Xin and Chen, Shuai-Yu and Lian, Hui-Wen and Deng, Yang and Duan, Rui and Zhang, Ying-Dong and Jiang, Teng},
title = {{The TREM2 H157Y Variant Influences Microglial Phagocytosis, Polarization, and Inflammatory Cytokine Release}},
journal = {Brain sciences},
year = {2023},
doi = {10.3390/brainsci13040642},
pmid = {37190607},
url = {https://doi.org/10.3390/brainsci13040642}
}
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