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White matter aging drives microglial diversity
Safaiyan S, Besson-Girard S, Kaya T, Cantuti-Castelvetri L, Liu L, Ji H, Schifferer M, Gouna G et al.. Neuron, 2021-02-18
Topic: Brain proteins, microglia and lab models
Aging results in gray and white matter degeneration, but the specific microglial responses are unknown. Using single-cell RNA sequencing from white and gray matter separately, we identified white matter-associated microglia (WAMs), which share parts of the disease-associated microglia (DAM) gene signature and are characterized by activation of genes implicated in phagocytic activity and lipid metabolism. WAMs depend on triggering receptor expressed on myeloid cells 2 (TREM2) signaling and are aging dependent.
Key findings
- Using single-cell RNA sequencing from white and gray matter separately, we identified white matter-associated microglia (WAMs), which share parts of the disease-associated microglia (DAM) gene signature and are characterized by activation of genes implicated in phagocytic activity and lipid metabolism.
- WAMs depend on triggering receptor expressed on myeloid cells 2 (TREM2) signaling and are aging dependent.
- In the aged brain, WAMs form independent of apolipoprotein E (APOE), in contrast to mouse models of Alzheimer's disease, in which microglia with the WAM gene signature are generated prematurely and in an APOE-dependent pathway similar to DAMs.
- Within the white matter, microglia frequently cluster in nodules, where they are engaged in clearing degenerated myelin.
Why it matters
This work identifies white matter-associated microglia that depend on TREM2 signaling and increase with aging. It describes an aging-related microglial state but does not test any way to treat or prevent Alzheimer's.
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Study details
- Evidence strengthLow
How this study scored 56/100
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 | 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 | 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 470 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 67.1 citations a year over 7 year(s) since 2021 |
| Impact for its field and year | 5 / 6 | Cited 26.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 14 other studies in this library |
| Still being cited | 4 / 4 | Cited 259 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Mikael Simons: h-index 86 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Ludwig-Maximilians-Universität München: institution h-index 1,224 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 7 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 33606969) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 56 / 100 | — |
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Read the original
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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
Safaiyan, S., Besson-Girard, S., Kaya, T., Cantuti-Castelvetri, L., Liu, L., Ji, H., et al. (2021). White matter aging drives microglial diversity. Neuron. https://doi.org/10.1016/j.neuron.2021.01.027
Vancouver
Safaiyan S, Besson-Girard S, Kaya T, Cantuti-Castelvetri L, Liu L, Ji H, et al. White matter aging drives microglial diversity. Neuron. 2021. doi:10.1016/j.neuron.2021.01.027. PMID: 33606969.
BibTeX
@article{safaiyan2021-33606969,
author = {Safaiyan, S. and Besson-Girard, S. and Kaya, T. and Cantuti-Castelvetri, L. and Liu, L. and Ji, H. and Schifferer, M. and Gouna, G. and others},
title = {{White matter aging drives microglial diversity}},
journal = {Neuron},
year = {2021},
doi = {10.1016/j.neuron.2021.01.027},
pmid = {33606969},
url = {https://doi.org/10.1016/j.neuron.2021.01.027}
}
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