Microglia in Alzheimer's disease at single-cell level. Are there common patterns in humans and mice?
Chen Y, Colonna M.. The Journal of experimental medicine, 2021-07-22
Topic: Inflammation, microglia and astrocytes
Alzheimer's disease (AD) is characterized by extracellular aggregates of amyloid β peptides, intraneuronal tau aggregates, and neuronal death. This pathology triggers activation of microglia. Because variants of genes expressed in microglia correlate with AD risk, microglial response to pathology plausibly impacts disease course. In mouse AD models, single-cell RNA sequencing (scRNA-seq) analyses delineated this response as progressive conversion of homeostatic microglia into disease-associated microglia (DAM); additional reactive microglial populations have been reported in other models of neurodegeneration and neuroinflammation. We review all of these microglial signatures, highlighting four fundamental patterns: DAM, IFN-microglia, MHC-II microglia, and proliferating microglia. We propose that all reported microglia populations are either just one or a combination, depending on the clustering strategy applied and the disease model. We further review single-nucleus RNA sequencing (snRNA-seq) data from human AD specimens and discuss reasons for parallels and discrepancies between human and mouse transcriptional profiles. Finally, we outline future directions for delineating the microglial impact in AD pathogenesis.
Key findings
- In mouse AD models, single-cell RNA sequencing (scRNA-seq) analyses delineated this response as progressive conversion of homeostatic microglia into disease-associated microglia (DAM); additional reactive microglial populations have been reported in other models of neurodegeneration and neuroinflammation.
- We review all of these microglial signatures, highlighting four fundamental patterns: DAM, IFN-microglia, MHC-II microglia, and proliferating microglia.
- We propose that all reported microglia populations are either just one or a combination, depending on the clustering strategy applied and the disease model.
- We further review single-nucleus RNA sequencing (snRNA-seq) data from human AD specimens and discuss reasons for parallels and discrepancies between human and mouse transcriptional profiles.
- Finally, we outline future directions for delineating the microglial impact in AD pathogenesis.
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Study details
- Evidence strengthLow
How this study scored 43/100
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. 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 and multi-centre collaboration, so those were left out: it earned 25 of the 58 points we could judge it on, which is 43 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The Journal of experimental medicine) |
| 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 | 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 “mice”) — scores zero |
| 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 34292312) |
| Free to read | 2 / 2 | Free to read |
| Points | 25 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 25 of the 58 points we could judge it on is 43 out of 100. |
| Total | 43 / 100 | — |
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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APA 7th
Chen, Y., & Colonna, M. (2021). Microglia in Alzheimer's disease at single-cell level. Are there common patterns in humans and mice? The Journal of experimental medicine. https://doi.org/10.1084/jem.20202717
Vancouver
Chen Y, Colonna M. Microglia in Alzheimer's disease at single-cell level. Are there common patterns in humans and mice? The Journal of experimental medicine. 2021. doi:10.1084/jem.20202717. PMID: 34292312.
BibTeX
@article{chen2021-34292312,
author = {Chen, Y. and Colonna, M.},
title = {{Microglia in Alzheimer's disease at single-cell level. Are there common patterns in humans and mice?}},
journal = {The Journal of experimental medicine},
year = {2021},
doi = {10.1084/jem.20202717},
pmid = {34292312},
url = {https://doi.org/10.1084/jem.20202717}
}
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