Perivascular cells induce microglial phagocytic states and synaptic engulfment via SPP1 in mouse models of Alzheimer's disease
De Schepper S, Ge JZ, Sierksma A, Crowley G, Ferreira LSS, Garceau D, Toomey CE, Sokolova D et al.. Nature neuroscience, 2023-02-06
Topic: Inflammation, microglia and astrocytes
Alzheimer's disease (AD) is characterized by synaptic loss, which can result from dysfunctional microglial phagocytosis and complement activation. However, what signals drive aberrant microglia-mediated engulfment of synapses in AD is unclear. Here we report that secreted phosphoprotein 1 (SPP1/osteopontin) is upregulated predominantly by perivascular macrophages and, to a lesser extent, by perivascular fibroblasts. Perivascular SPP1 is required for microglia to engulf synapses and upregulate phagocytic markers including C1qa, Grn and Ctsb in presence of amyloid-β oligomers. Absence of Spp1 expression in AD mouse models results in prevention of synaptic loss. Furthermore, single-cell RNA sequencing and putative cell-cell interaction analyses reveal that perivascular SPP1 induces microglial phagocytic states in the hippocampus of a mouse model of AD. Altogether, we suggest a functional role for SPP1 in perivascular cells-to-microglia crosstalk, whereby SPP1 modulates microglia-mediated synaptic engulfment in mouse models of AD.
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APA 7th
De Schepper, S., Ge, J. Z., Sierksma, A., Crowley, G., Ferreira, L. S. S., Garceau, D., et al. (2023). Perivascular cells induce microglial phagocytic states and synaptic engulfment via SPP1 in mouse models of Alzheimer's disease. Nature neuroscience. https://doi.org/10.1038/s41593-023-01257-z
Vancouver
De Schepper S, Ge JZ, Sierksma A, Crowley G, Ferreira LSS, Garceau D, et al. Perivascular cells induce microglial phagocytic states and synaptic engulfment via SPP1 in mouse models of Alzheimer's disease. Nature neuroscience. 2023. doi:10.1038/s41593-023-01257-z. PMID: 36747024.
BibTeX
@article{deschepper2023-36747024,
author = {De Schepper, S. and Ge, J. Z. and Sierksma, A. and Crowley, G. and Ferreira, L. S. S. and Garceau, D. and Toomey, C. E. and Sokolova, D. and others},
title = {{Perivascular cells induce microglial phagocytic states and synaptic engulfment via SPP1 in mouse models of Alzheimer's disease}},
journal = {Nature neuroscience},
year = {2023},
doi = {10.1038/s41593-023-01257-z},
pmid = {36747024},
url = {https://doi.org/10.1038/s41593-023-01257-z}
}
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Key findings
- Alzheimer's disease (AD) is characterized by synaptic loss, which can result from dysfunctional microglial phagocytosis and complement activation.
- Absence of Spp1 expression in AD mouse models results in prevention of synaptic loss.
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Study details
- Evidence strengthLow
How this study scored 47/100
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 and multi-centre collaboration, so those were left out: it earned 27 of the 58 points we could judge it on, which is 47 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Nature neuroscience) |
| 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 | 2023 — 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 “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 36747024) |
| Free to read | 2 / 2 | Free to read |
| Points | 27 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 27 of the 58 points we could judge it on is 47 out of 100. |
| Total | 47 / 100 | — |
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