Comprehensive single-cell transcriptomic atlas of microglia in Alzheimer's disease mouse models
Ping Liu, Tingfang Sun, Jie Yang, Hongrui Li, Wanwan Min, Xingyu Zhou, Ruihan Xiong, Jing Wu et al.. Molecular psychiatry, 2026-03-21
Topic: Inflammation, microglia and astrocytes
Microglia are central mediators of neuroinflammation in Alzheimer's disease (AD), yet conserved microglial states and activation trajectories across AD mouse models remain incompletely defined. Here, we constructed a comprehensive Mouse Microglia Atlas (MoMicA) to resolve conserved subtypes, delineate dynamic trajectories, and identify key regulators associated with AD pathology. We integrated ten single-cell and single-nucleus RNA-sequencing datasets from major AD mouse models, yielding 84,764 microglia for harmonized clustering, co-expression network analysis, and pseudotime inference, complemented by immune staining. Across models, AD was characterized by contraction of homeostatic microglia and marked expansion of DAM. MoMicA further delineated refined homeostatic and disease-associated subpopulations, including different homeostatic microglia subclusters and a stepwise progression from homeostatic microglia through activated response and pre-disease-associated states to disease-associated microglia. Network analysis highlighted lipid metabolism and inflammation as dominant AD-related programs and identified Fabp5 as a central hub gene within a DAM-associated lipid module. Multiplex immunofluorescence confirmed that Fabp5 is induced in Clec7a-positive DAM around amyloid plaques in two amyloidosis models. MoMicA therefore provides a valuable resource for dissecting the mechanistic roles of microglia in the onset and progression of AD.
Key findings
- Here, we constructed a comprehensive Mouse Microglia Atlas (MoMicA) to resolve conserved subtypes, delineate dynamic trajectories, and identify key regulators associated with AD pathology.
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Study details
- Evidence strengthLow
How this study scored 48/100
Published in a leading specialty 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, multi-centre collaboration and free to read, so those were left out: it earned 27 of the 56 points we could judge it on, which is 48 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Molecular psychiatry) |
| 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 | 5 / 5 | 2026 — within 1 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 | 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 41865123) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 27 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 27 of the 56 points we could judge it on is 48 out of 100. |
| Total | 48 / 100 | — |
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APA 7th
Liu, P., Sun, T., Yang, J., Li, H., Min, W., Zhou, X., et al. (2026). Comprehensive single-cell transcriptomic atlas of microglia in Alzheimer's disease mouse models. Molecular psychiatry. https://doi.org/10.1038/s41380-026-03529-z
Vancouver
Liu P, Sun T, Yang J, Li H, Min W, Zhou X, et al. Comprehensive single-cell transcriptomic atlas of microglia in Alzheimer's disease mouse models. Molecular psychiatry. 2026. doi:10.1038/s41380-026-03529-z. PMID: 41865123.
BibTeX
@article{liu2026-41865123,
author = {Liu, Ping and Sun, Tingfang and Yang, Jie and Li, Hongrui and Min, Wanwan and Zhou, Xingyu and Xiong, Ruihan and Wu, Jing and others},
title = {{Comprehensive single-cell transcriptomic atlas of microglia in Alzheimer's disease mouse models}},
journal = {Molecular psychiatry},
year = {2026},
doi = {10.1038/s41380-026-03529-z},
pmid = {41865123},
url = {https://doi.org/10.1038/s41380-026-03529-z}
}