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TREM2 ameliorates neuroinflammatory response and cognitive impairment via PI3K/AKT/FoxO3a signaling pathway in Alzheimer's disease mice
Wang Y, Lin Y, Wang L, Zhan H, Luo X, Zeng Y, Wu W, Zhang X et al.. Aging, 2020-10-16
Topic: Brain proteins, microglia and lab models
Triggering receptor expressed on myeloid cells 2 (TREM2) has been shown with a neuroprotective function against inflammation and neuronal injury in Alzheimer's disease (AD). However, the TREM2 induced anti-inflammatory mechanism is still not well known. In this study it has been demonstrated that the expression of TREM2 was upregulated in hippocampus of 5xFAD mice, whereas TREM2 knock-out mediated by AAV significantly increased the levels of pro-inflammatory cytokines and aggravated cognitive defect.
Key findings
- However, the TREM2 induced anti-inflammatory mechanism is still not well known.
- In this study it has been demonstrated that the expression of TREM2 was upregulated in hippocampus of 5xFAD mice, whereas TREM2 knock-out mediated by AAV significantly increased the levels of pro-inflammatory cytokines and aggravated cognitive defect.
- Additionally, FoxO3a, a downstream member of the PI3K/AKT pathway, could be activated by TREM2 defect via the PI3K/AKT signaling in 5xFAD mice.
- That suggests TREM2-induced protection is associated with the PI3K-FoxO3a axis.
Why it matters
In Alzheimer's disease mice, removing TREM2 increased pro-inflammatory cytokines and worsened cognitive defects, while TREM2 appears to act through the PI3K/AKT/FoxO3a pathway. This is animal research only and does not show that targeting TREM2 would treat or prevent Alzheimer's disease in people.
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Study details
- Evidence strengthLow
How this study scored 48/100
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 (Aging) |
| Journal's citation record | 2 / 4 | Aging: journal h-index 162 (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 | 2020 — 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 | 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 | 5 / 7 | Cited 197 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 24.6 citations a year over 8 year(s) since 2020 |
| Impact for its field and year | 3 / 6 | Cited 5.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 10 other studies in this library |
| Still being cited | 3 / 4 | Cited 128 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Fang Wang: h-index 79 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | Southern Medical University: institution h-index 497 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 33065553) |
| Free to read | 2 / 2 | Free to read |
| Total | 48 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Wang, Y., Lin, Y., Wang, L., Zhan, H., Luo, X., Zeng, Y., et al. (2020). TREM2 ameliorates neuroinflammatory response and cognitive impairment via PI3K/AKT/FoxO3a signaling pathway in Alzheimer's disease mice. Aging. https://doi.org/10.18632/aging.104104
Vancouver
Wang Y, Lin Y, Wang L, Zhan H, Luo X, Zeng Y, et al. TREM2 ameliorates neuroinflammatory response and cognitive impairment via PI3K/AKT/FoxO3a signaling pathway in Alzheimer's disease mice. Aging. 2020. doi:10.18632/aging.104104. PMID: 33065553.
BibTeX
@article{wang2020-33065553,
author = {Wang, Y. and Lin, Y. and Wang, L. and Zhan, H. and Luo, X. and Zeng, Y. and Wu, W. and Zhang, X. and others},
title = {{TREM2 ameliorates neuroinflammatory response and cognitive impairment via PI3K/AKT/FoxO3a signaling pathway in Alzheimer's disease mice}},
journal = {Aging},
year = {2020},
doi = {10.18632/aging.104104},
pmid = {33065553},
url = {https://doi.org/10.18632/aging.104104}
}
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