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Natural genetic variation determines microglia heterogeneity in wild-derived mouse models of Alzheimer's disease
Yang HS, Onos KD, Choi K, Keezer KJ, Skelly DA, Carter GW, Howell GR.. Cell reports, 2021-02-01
Topic: Brain proteins, microglia and lab models
Genetic and genome-wide association studies suggest a central role for microglia in Alzheimer's disease (AD). However, single-cell RNA sequencing (scRNA-seq) of microglia in mice, a key preclinical model, has shown mixed results regarding translatability to human studies. To address this, scRNA-seq of microglia from C57BL/6J (B6) and wild-derived strains (WSB/EiJ, CAST/EiJ, and PWK/PhJ) with and without APP/PS1 demonstrates that genetic diversity significantly alters features and dynamics of microglia in baseline neuroimmune functions and in response to amyloidosis.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Yang, H. S., Onos, K. D., Choi, K., Keezer, K. J., Skelly, D. A., Carter, G. W., et al. (2021). Natural genetic variation determines microglia heterogeneity in wild-derived mouse models of Alzheimer's disease. Cell reports. https://doi.org/10.1016/j.celrep.2021.108739
Vancouver
Yang HS, Onos KD, Choi K, Keezer KJ, Skelly DA, Carter GW, et al. Natural genetic variation determines microglia heterogeneity in wild-derived mouse models of Alzheimer's disease. Cell reports. 2021. doi:10.1016/j.celrep.2021.108739. PMID: 33567283.
BibTeX
@article{yang2021-33567283,
author = {Yang, H. S. and Onos, K. D. and Choi, K. and Keezer, K. J. and Skelly, D. A. and Carter, G. W. and Howell, G. R.},
title = {{Natural genetic variation determines microglia heterogeneity in wild-derived mouse models of Alzheimer's disease}},
journal = {Cell reports},
year = {2021},
doi = {10.1016/j.celrep.2021.108739},
pmid = {33567283},
url = {https://doi.org/10.1016/j.celrep.2021.108739}
}
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.
Key findings
- However, single-cell RNA sequencing (scRNA-seq) of microglia in mice, a key preclinical model, has shown mixed results regarding translatability to human studies.
- To address this, scRNA-seq of microglia from C57BL/6J (B6) and wild-derived strains (WSB/EiJ, CAST/EiJ, and PWK/PhJ) with and without APP/PS1 demonstrates that genetic diversity significantly alters features and dynamics of microglia in baseline neuroimmune functions and in response to amyloidosis.
- Results show significant variation in the abundance of microglial subtypes or states, including numbers of previously identified disease-associated and interferon-responding microglia, across the strains.
- For each subtype, significant differences in the expression of many genes are observed in wild-derived strains relative to B6, including 19 genes previously associated with human AD including Apoe, Trem2, and Sorl1.
Why it matters
This study used single-cell RNA sequencing of microglia from different mouse strains with and without APP/PS1 to show that genetic diversity alters microglial features and responses to amyloidosis. It is animal research on microglial heterogeneity and does not test any treatment, cure, or prevention for Alzheimer's disease.
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Study details
- Evidence strengthLow
How this study scored 45/100
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 (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 | 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 “mouse”) — 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 70 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 10.0 citations a year over 7 year(s) since 2021 |
| Impact for its field and year | 3 / 6 | Cited 4.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 2 / 4 | Cited 32 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Gareth R. Howell: h-index 50 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Tufts University: institution h-index 1,045 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 33567283) |
| Free to read | 2 / 2 | Free to read |
| Total | 45 / 100 | — |
What each of these 20 components measures, and what this score is not →
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