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Elevated TREM2 Gene Dosage Reprograms Microglia Responsivity and Ameliorates Pathological Phenotypes in Alzheimer's Disease Models
Lee CYD, Daggett A, Gu X, Jiang LL, Langfelder P, Li X, Wang N, Zhao Y et al.. Neuron, 2018-03-01
Topic: Brain proteins, microglia and lab models
Variants of TREM2 are associated with Alzheimer's disease (AD). To study whether increasing TREM2 gene dosage could modify the disease pathogenesis, we developed BAC transgenic mice expressing human TREM2 (BAC-TREM2) in microglia. We found that elevated TREM2 expression reduced amyloid burden in the 5xFAD mouse model.
Key findings
- To study whether increasing TREM2 gene dosage could modify the disease pathogenesis, we developed BAC transgenic mice expressing human TREM2 (BAC-TREM2) in microglia.
- We found that elevated TREM2 expression reduced amyloid burden in the 5xFAD mouse model.
- Transcriptomic profiling demonstrated that increasing TREM2 levels conferred a rescuing effect, which includes dampening the expression of multiple disease-associated microglial genes and augmenting downregulated neuronal genes.
- Interestingly, 5xFAD/BAC-TREM2 mice showed further upregulation of several reactive microglial genes linked to phagocytosis and negative regulation of immune cell activation.
Why it matters
In 5xFAD mice, raising TREM2 gene dosage reduced amyloid burden and changed microglial and neuronal gene expression. This is animal work, so it does not show that increasing TREM2 helps people with Alzheimer's.
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Study details
- Evidence strengthLow
How this study scored 53/100
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 (Neuron) |
| Journal's citation record | 4 / 4 | Neuron: journal h-index 689 (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 | 2018 — 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 | 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 | 6 / 7 | Cited 396 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 39.6 citations a year over 10 year(s) since 2018 |
| Impact for its field and year | 4 / 6 | Cited 14.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 70 other studies in this library |
| Still being cited | 3 / 4 | Cited 145 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author X. William Yang: h-index 53 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of California, Los Angeles: institution h-index 1,923 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 29518357) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 53 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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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'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
Lee, C. Y. D., Daggett, A., Gu, X., Jiang, L. L., Langfelder, P., Li, X., et al. (2018). Elevated TREM2 Gene Dosage Reprograms Microglia Responsivity and Ameliorates Pathological Phenotypes in Alzheimer's Disease Models. Neuron. https://doi.org/10.1016/j.neuron.2018.02.002
Vancouver
Lee CYD, Daggett A, Gu X, Jiang LL, Langfelder P, Li X, et al. Elevated TREM2 Gene Dosage Reprograms Microglia Responsivity and Ameliorates Pathological Phenotypes in Alzheimer's Disease Models. Neuron. 2018. doi:10.1016/j.neuron.2018.02.002. PMID: 29518357.
BibTeX
@article{lee2018-29518357,
author = {Lee, C. Y. D. and Daggett, A. and Gu, X. and Jiang, L. L. and Langfelder, P. and Li, X. and Wang, N. and Zhao, Y. and others},
title = {{Elevated TREM2 Gene Dosage Reprograms Microglia Responsivity and Ameliorates Pathological Phenotypes in Alzheimer's Disease Models}},
journal = {Neuron},
year = {2018},
doi = {10.1016/j.neuron.2018.02.002},
pmid = {29518357},
url = {https://doi.org/10.1016/j.neuron.2018.02.002}
}
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