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Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and TREM2-independent cellular responses in Alzheimer's disease
Zhou Y, Song WM, Andhey PS, Swain A, Levy T, Miller KR, Poliani PL, Cominelli M et al.. Nature medicine, 2020-01-13
Topic: Brain proteins, microglia and lab models
Glia have been implicated in Alzheimer's disease (AD) pathogenesis. Variants of the microglia receptor triggering receptor expressed on myeloid cells 2 (TREM2) increase AD risk, and activation of disease-associated microglia (DAM) is dependent on TREM2 in mouse models of AD. We surveyed gene-expression changes associated with AD pathology and TREM2 in 5XFAD mice and in human AD by single-nucleus RNA sequencing.
Key findings
- Variants of the microglia receptor triggering receptor expressed on myeloid cells 2 (TREM2) increase AD risk, and activation of disease-associated microglia (DAM) is dependent on TREM2 in mouse models of AD.
- We surveyed gene-expression changes associated with AD pathology and TREM2 in 5XFAD mice and in human AD by single-nucleus RNA sequencing.
- We confirmed the presence of Trem2-dependent DAM and identified a previously undiscovered Serpina3n + C4b + reactive oligodendrocyte population in mice.
- Interestingly, remarkably different glial phenotypes were evident in human AD.
Why it matters
Using single-nucleus RNA sequencing, a way of reading which genes are active in individual brain cells, the study looked at brain tissue from an Alzheimer's mouse model (5XFAD) and from people with Alzheimer's. In the mice it confirmed TREM2-dependent "disease-associated microglia" and reported a previously undescribed Serpina3n+ C4b+ reactive oligodendrocyte population, but it reported "remarkably different glial phenotypes" in human Alzheimer's tissue. It is a descriptive laboratory study that does not test a treatment, and its mouse findings should not be assumed to apply to people.
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Study details
- Evidence strengthLow
How this study scored 66/100
Published in a top-tier 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 | 10 / 10 | Tier 1 — top-tier general journal (Nature medicine) |
| Journal's citation record | 4 / 4 | Nature Medicine: journal h-index 763 (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 “mouse”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 7 / 7 | Cited 1,144 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 143.0 citations a year over 8 year(s) since 2020 |
| Impact for its field and year | 6 / 6 | Cited 50.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 76 other studies in this library |
| Still being cited | 4 / 4 | Cited 533 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Marco Colonna: h-index 172 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Washington University in St. Louis: institution h-index 1,962 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 10 institution(s) in 4 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 31932797) |
| Free to read | 2 / 2 | Free to read |
| Total | 66 / 100 | — |
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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
Zhou, Y., Song, W. M., Andhey, P. S., Swain, A., Levy, T., Miller, K. R., et al. (2020). Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and TREM2-independent cellular responses in Alzheimer's disease. Nature medicine. https://doi.org/10.1038/s41591-019-0695-9
Vancouver
Zhou Y, Song WM, Andhey PS, Swain A, Levy T, Miller KR, et al. Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and TREM2-independent cellular responses in Alzheimer's disease. Nature medicine. 2020. doi:10.1038/s41591-019-0695-9. PMID: 31932797.
BibTeX
@article{zhou2020-31932797,
author = {Zhou, Y. and Song, W. M. and Andhey, P. S. and Swain, A. and Levy, T. and Miller, K. R. and Poliani, P. L. and Cominelli, M. and others},
title = {{Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and TREM2-independent cellular responses in Alzheimer's disease}},
journal = {Nature medicine},
year = {2020},
doi = {10.1038/s41591-019-0695-9},
pmid = {31932797},
url = {https://doi.org/10.1038/s41591-019-0695-9}
}
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