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Microglia-synapse engulfment via PtdSer-TREM2 ameliorates neuronal hyperactivity in Alzheimer's disease models
Rueda-Carrasco J, Sokolova D, Lee SE, Childs T, Jurčáková N, Crowley G, De Schepper S, Ge JZ et al.. The EMBO journal, 2023-08-14
Topic: Brain proteins, microglia and lab models
Neuronal hyperactivity is a key feature of early stages of Alzheimer's disease (AD). Genetic studies in AD support that microglia act as potential cellular drivers of disease risk, but the molecular determinants of microglia-synapse engulfment associated with neuronal hyperactivity in AD are unclear. Here, using super-resolution microscopy, 3D-live imaging of co-cultures, and in vivo imaging of lipids in genetic models, we found that spines become hyperactive upon Aβ oligomer stimulation and externalize phosphatidylserine (ePtdSer), a canonical "eat-me" signal.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Rueda-Carrasco, J., Sokolova, D., Lee, S. E., Childs, T., Jurčáková, N., Crowley, G., et al. (2023). Microglia-synapse engulfment via PtdSer-TREM2 ameliorates neuronal hyperactivity in Alzheimer's disease models. The EMBO journal. https://doi.org/10.15252/embj.2022113246
Vancouver
Rueda-Carrasco J, Sokolova D, Lee SE, Childs T, Jurčáková N, Crowley G, et al. Microglia-synapse engulfment via PtdSer-TREM2 ameliorates neuronal hyperactivity in Alzheimer's disease models. The EMBO journal. 2023. doi:10.15252/embj.2022113246. PMID: 37575021.
BibTeX
@article{ruedacarrasco2023-37575021,
author = {Rueda-Carrasco, J. and Sokolova, D. and Lee, S. E. and Childs, T. and Jurčáková, N. and Crowley, G. and De Schepper, S. and Ge, J. Z. and others},
title = {{Microglia-synapse engulfment via PtdSer-TREM2 ameliorates neuronal hyperactivity in Alzheimer's disease models}},
journal = {The EMBO journal},
year = {2023},
doi = {10.15252/embj.2022113246},
pmid = {37575021},
url = {https://doi.org/10.15252/embj.2022113246}
}
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Key findings
- Genetic studies in AD support that microglia act as potential cellular drivers of disease risk, but the molecular determinants of microglia-synapse engulfment associated with neuronal hyperactivity in AD are unclear.
- Here, using super-resolution microscopy, 3D-live imaging of co-cultures, and in vivo imaging of lipids in genetic models, we found that spines become hyperactive upon Aβ oligomer stimulation and externalize phosphatidylserine (ePtdSer), a canonical "eat-me" signal.
- These apoptotic-like spines are targeted by microglia for engulfment via TREM2 leading to amelioration of Aβ oligomer-induced synaptic hyperactivity.
- We also show the in vivo relevance of ePtdSer-TREM2 signaling in microglia-synapse engulfment in the hAPP NL-F knock-in mouse model of AD.
Why it matters
In cell and animal models, amyloid-beta oligomers made spines hyperactive and exposed phosphatidylserine, which microglia then recognized through TREM2. This is early laboratory work and does not establish a treatment, cure, or prevention for Alzheimer's disease in people.
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Study details
- Evidence strengthLow
How this study scored 55/100
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 (The EMBO journal) |
| Journal's citation record | 4 / 4 | The EMBO Journal: journal h-index 563 (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 | 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 | 5 / 7 | Cited 122 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 24.4 citations a year over 5 year(s) since 2023 |
| Impact for its field and year | 4 / 6 | Cited 10.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 5 other studies in this library |
| Still being cited | 3 / 4 | Cited 116 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Soyon Hong: h-index 29 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 12 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 37575021) |
| Free to read | 2 / 2 | Free to read |
| Total | 55 / 100 | — |
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