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VEGF controls microglial phagocytic response to amyloid-β
Priscille de Gea, Sarah Benkeder, Pauline Bouvet, Mélanie Aimard, Naura Chounlamountri, Jérôme Honnorat, Le Duy Do, Claire Meissirel. Frontiers in cellular neuroscience, 2023-12-15
Topic: Inflammation, microglia and astrocytes
Microglial cells are well known to be implicated in the pathogenesis of Alzheimer's disease (AD), due to the impaired clearance of amyloid-β (Aβ) protein. In AD, Aβ accumulates in the brain parenchyma as soluble oligomers and protofibrils, and its aggregation process further give rise to amyloid plaques. Compelling evidence now indicate that Aβ oligomers (Aβo) are the most toxic forms responsible for neuronal and synaptic alterations. Recently, we showed that the Vascular Endothelial Growth Factor (VEGF) counteracts Aβo-induced synaptic alterations and that a peptide derived from VEGF is able to inhibit Aβ aggregation process. Moreover, VEGF has been reported to promote microglial chemotaxis to Aβ brain deposits. We therefore investigated whether VEGF could influence microglial phagocytic response to Aβ, using in vitro and ex vivo models of amyloid accumulation. We report here that VEGF increases Aβo phagocytosis by microglial cells and further characterized the molecular basis of the VEGF effect. VEGF is able to control α-secretase activity in microglial cells, resulting in the increased cleavage of the Triggering Receptor Expressed on Myeloid cells 2 (TREM2), a major microglial Aβ receptor. Consistently, the soluble form sTREM2 also increases Aβo phagocytosis by microglial cells. Taken together, these findings propose VEGF as a new regulator of Aβ clearance and suggest its potential role in rescuing compromised microglial function in AD.
Key findings
- Compelling evidence now indicate that Aβ oligomers (Aβo) are the most toxic forms responsible for neuronal and synaptic alterations.
- Recently, we showed that the Vascular Endothelial Growth Factor (VEGF) counteracts Aβo-induced synaptic alterations and that a peptide derived from VEGF is able to inhibit Aβ aggregation process.
- Taken together, these findings propose VEGF as a new regulator of Aβ clearance and suggest its potential role in rescuing compromised microglial function in AD.
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Study details
- Evidence strengthLow
How this study scored 41/100
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. 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 23 of the 56 points we could judge it on, which is 41 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Frontiers in cellular 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 | 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 | — / 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 38162003) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 23 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 23 of the 56 points we could judge it on is 41 out of 100. |
| Total | 41 / 100 | — |
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Read the original
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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 names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
de Gea, P., Benkeder, S., Bouvet, P., Aimard, M., Chounlamountri, N., Honnorat, J., et al. (2023). VEGF controls microglial phagocytic response to amyloid-β. Frontiers in cellular neuroscience. https://doi.org/10.3389/fncel.2023.1264402
Vancouver
de Gea P, Benkeder S, Bouvet P, Aimard M, Chounlamountri N, Honnorat J, et al. VEGF controls microglial phagocytic response to amyloid-β. Frontiers in cellular neuroscience. 2023. doi:10.3389/fncel.2023.1264402. PMID: 38162003.
BibTeX
@article{degea2023-38162003,
author = {de Gea, Priscille and Benkeder, Sarah and Bouvet, Pauline and Aimard, Mélanie and Chounlamountri, Naura and Honnorat, Jérôme and Do, Le Duy and Meissirel, Claire},
title = {{VEGF controls microglial phagocytic response to amyloid-β}},
journal = {Frontiers in cellular neuroscience},
year = {2023},
doi = {10.3389/fncel.2023.1264402},
pmid = {38162003},
url = {https://doi.org/10.3389/fncel.2023.1264402}
}
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