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Single-nucleus transcriptomics reveals a distinct microglial state and increased MSR1-mediated phagocytosis as common features across dementia subtypes
Sook‐Yoong Chia, Mengwei Li, Zigang Li, Haitao Tu, Jolene Wei Ling Lee, Lifeng Qiu, Jingjing Ling, Richard J. Reynolds et al.. Genome Medicine, 2025-08-18
Topic: Brain proteins, microglia and lab models
SnRNA-seq analysis revealed elevated microglial proportions across all dementia subtypes compared to NCI. Further analysis of cell type-specific transcriptomes identified overlapping differentially expressed genes (DEGs) between microglia and oligodendrocytes across all dementia subtypes. While AD showed molecular similarities to NCI, PDD and DLB were clustered more closely together, sharing a greater number of DEGs and related pathways, predominantly associated with microglia. Investigation of interactions between microglia and oligodendrocytes revealed a distinct microglial state in all dementia subtypes. MSR1, a gene encoding a scavenger receptor, was upregulated in microglia across all dementia subtypes, along with its associated gene HSPA1A in oligodendrocytes. RNAscope supported the potential interaction between microglia and oligodendrocytes, where these cells were in closer proximity to each other in human cortical tissues of PDD compared to NCI. MSR1 expression was significantly increased in cortical primary microglia from PD mice compared with non-transgenic (NTg) mice. Additionally, the expression of myelin-associated genes (MBP, MOBP, and PLP1) was significantly upregulated in PD microglia compared to NTg, supporting the presence of the distinct microglia. Furthermore, MSR1-positive microglia colocalised with MBP in cortical tissue of PDD patients, suggesting a functional role of MSR1 in myelin debris clearance. Overexpression of MSR1 in microglial cells enhanced their phagocytic activity toward myelin, and reciprocally, myelin treatment upregulated MSR1 protein levels, indicating enhanced MSR1-mediated myelin phagocytosis. Our findings provide novel insights into the cell type-specific role of microglial MSR1 in AD, DLB, and PDD, linking its increased phagocytic capacity to myelin defects as a common feature of neurodegenerative dementias.
Key findings
- SnRNA-seq analysis revealed elevated microglial proportions across all dementia subtypes compared to NCI.
- Further analysis of cell type-specific transcriptomes identified overlapping differentially expressed genes (DEGs) between microglia and oligodendrocytes across all dementia subtypes.
- While AD showed molecular similarities to NCI, PDD and DLB were clustered more closely together, sharing a greater number of DEGs and related pathways, predominantly associated with microglia.
- Investigation of interactions between microglia and oligodendrocytes revealed a distinct microglial state in all dementia subtypes.
- MSR1, a gene encoding a scavenger receptor, was upregulated in microglia across all dementia subtypes, along with its associated gene HSPA1A in oligodendrocytes.
Why it matters
Analysis of brain tissue from several dementia subtypes found increased microglia and a distinct microglial state with higher MSR1-mediated phagocytosis, including in Parkinson's disease dementia and dementia with Lewy bodies. This describes a shared feature across dementias but does not report a treatment or cure.
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, 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 (Genome Medicine) |
| Journal's citation record | 2 / 4 | Genome Medicine: journal h-index 174 (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 | 4 / 5 | 2025 — within 3 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 | 3 / 7 | Cited 15 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 5.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 3 / 6 | Cited 4.6× 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 15 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Li Zeng: h-index 35 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Imperial College London: institution h-index 1,744 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 10 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40826098) |
| Free to read | 2 / 2 | Free to read |
| Total | 45 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1186/s13073-025-01519-4
- PubMed: 40826098
- Original source →
- Free full text: Genome Medicine →
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
Chia, S., Li, M., Li, Z., Tu, H., Lee, J. W. L., Qiu, L., et al. (2025). Single-nucleus transcriptomics reveals a distinct microglial state and increased MSR1-mediated phagocytosis as common features across dementia subtypes. Genome Medicine. https://doi.org/10.1186/s13073-025-01519-4
Vancouver
Chia S, Li M, Li Z, Tu H, Lee JWL, Qiu L, et al. Single-nucleus transcriptomics reveals a distinct microglial state and increased MSR1-mediated phagocytosis as common features across dementia subtypes. Genome Medicine. 2025. doi:10.1186/s13073-025-01519-4. PMID: 40826098.
BibTeX
@article{chia2025-40826098,
author = {Chia, Sook‐Yoong and Li, Mengwei and Li, Zigang and Tu, Haitao and Lee, Jolene Wei Ling and Qiu, Lifeng and Ling, Jingjing and Reynolds, Richard J. and others},
title = {{Single-nucleus transcriptomics reveals a distinct microglial state and increased MSR1-mediated phagocytosis as common features across dementia subtypes}},
journal = {Genome Medicine},
year = {2025},
doi = {10.1186/s13073-025-01519-4},
pmid = {40826098},
url = {https://doi.org/10.1186/s13073-025-01519-4}
}
Studies this one cites
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