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Differential interaction with TREM2 modulates microglial uptake of modified Aβ species
Pranav Joshi, Florian Riffel, Kanayo Satoh, Masahiro Enomoto, Seema Qamar, Hannah Scheiblich, Nàdia Villacampa, Sathish Kumar et al.. Glia, 2021-08-24
Topic: Inflammation, microglia and astrocytes
Rare coding variants of the microglial triggering receptor expressed on myeloid cells 2 (TREM2) confer an increased risk for Alzheimer's disease (AD) characterized by the progressive accumulation of aggregated forms of amyloid β peptides (Aβ). Aβ peptides are generated by proteolytic processing of the amyloid precursor protein (APP). Heterogeneity in proteolytic cleavages and additional post-translational modifications result in the production of several distinct Aβ variants that could differ in their aggregation behavior and toxic properties. Here, we sought to assess whether post-translational modifications of Aβ affect the interaction with TREM2. Biophysical and biochemical methods revealed that TREM2 preferentially interacts with oligomeric Aβ, and that phosphorylation of Aβ increases this interaction. Phosphorylation of Aβ also affected the TREM2 dependent interaction and phagocytosis by primary microglia and in APP transgenic mouse models. Thus, TREM2 function is important for sensing phosphorylated Aβ variants in distinct aggregation states and reduces the accumulation and deposition of these toxic Aβ species in preclinical models of Alzheimer's disease.
Key findings
- Rare coding variants of the microglial triggering receptor expressed on myeloid cells 2 (TREM2) confer an increased risk for Alzheimer's disease (AD) characterized by the progressive accumulation of aggregated forms of amyloid β peptides (Aβ).
- Heterogeneity in proteolytic cleavages and additional post-translational modifications result in the production of several distinct Aβ variants that could differ in their aggregation behavior and toxic properties.
- Biophysical and biochemical methods revealed that TREM2 preferentially interacts with oligomeric Aβ, and that phosphorylation of Aβ increases this interaction.
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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 (Glia) |
| 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 | 2021 — 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 34427354) |
| 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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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
Joshi, P., Riffel, F., Satoh, K., Enomoto, M., Qamar, S., Scheiblich, H., et al. (2021). Differential interaction with TREM2 modulates microglial uptake of modified Aβ species. Glia. https://doi.org/10.1002/glia.24077
Vancouver
Joshi P, Riffel F, Satoh K, Enomoto M, Qamar S, Scheiblich H, et al. Differential interaction with TREM2 modulates microglial uptake of modified Aβ species. Glia. 2021. doi:10.1002/glia.24077. PMID: 34427354.
BibTeX
@article{joshi2021-34427354,
author = {Joshi, Pranav and Riffel, Florian and Satoh, Kanayo and Enomoto, Masahiro and Qamar, Seema and Scheiblich, Hannah and Villacampa, Nàdia and Kumar, Sathish and others},
title = {{Differential interaction with TREM2 modulates microglial uptake of modified Aβ species}},
journal = {Glia},
year = {2021},
doi = {10.1002/glia.24077},
pmid = {34427354},
url = {https://doi.org/10.1002/glia.24077}
}
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