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High-affinity interactions and signal transduction between Aβ oligomers and TREM2
Lessard CB, Malnik SL, Zhou Y, Ladd TB, Cruz PE, Ran Y, Mahan TE, Chakrabaty P et al.. EMBO molecular medicine, 2018-11-01
Topic: Brain proteins, microglia and lab models
Rare coding variants in the triggering receptor expressed on myeloid cells 2 (TREM2) are associated with increased risk for Alzheimer's disease (AD), but how they confer this risk remains uncertain. We assessed binding of TREM2, AD-associated TREM2 variants to various forms of Aβ and APOE in multiple assays. TREM2 interacts directly with various forms of Aβ, with highest affinity interactions observed between TREM2 and soluble Aβ42 oligomers.
Key findings
- We assessed binding of TREM2, AD-associated TREM2 variants to various forms of Aβ and APOE in multiple assays.
- TREM2 interacts directly with various forms of Aβ, with highest affinity interactions observed between TREM2 and soluble Aβ42 oligomers.
- High-affinity binding of TREM2 to Aβ oligomers is characterized by very slow dissociation.
- Pre-incubation with Aβ is shown to block the interaction of APOE In cellular assays, AD-associated variants of TREM2 reduced the amount of Aβ42 internalized, and in NFAT assay, the R47H and R62H variants decreased NFAT signaling activity in response to Aβ42.
Why it matters
In laboratory assays, TREM2 bound directly to forms of amyloid-beta, especially soluble oligomers, and Alzheimer's-linked TREM2 variants reduced how much amyloid-beta was taken into cells. This is laboratory work and does not show that targeting this interaction treats or prevents Alzheimer's disease.
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Study details
- Evidence strengthLow
How this study scored 50/100
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 (EMBO molecular medicine) |
| Journal's citation record | 2 / 4 | EMBO Molecular Medicine: journal h-index 186 (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 | 2 / 5 | 2018 — within 10 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 155 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 15.5 citations a year over 10 year(s) since 2018 |
| Impact for its field and year | 3 / 6 | Cited 7.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 29 other studies in this library |
| Still being cited | 3 / 4 | Cited 62 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Todd Eliot Golde: h-index 111 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Washington University in St. Louis: institution h-index 1,962 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 30341064) |
| Free to read | 2 / 2 | Free to read |
| Total | 50 / 100 | — |
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Read the original
- DOI: 10.15252/emmm.201809027
- PubMed: 30341064
- Original source →
- Free full text: EMBO Molecular 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
Lessard, C. B., Malnik, S. L., Zhou, Y., Ladd, T. B., Cruz, P. E., Ran, Y., et al. (2018). High-affinity interactions and signal transduction between Aβ oligomers and TREM2. EMBO molecular medicine. https://doi.org/10.15252/emmm.201809027
Vancouver
Lessard CB, Malnik SL, Zhou Y, Ladd TB, Cruz PE, Ran Y, et al. High-affinity interactions and signal transduction between Aβ oligomers and TREM2. EMBO molecular medicine. 2018. doi:10.15252/emmm.201809027. PMID: 30341064.
BibTeX
@article{lessard2018-30341064,
author = {Lessard, C. B. and Malnik, S. L. and Zhou, Y. and Ladd, T. B. and Cruz, P. E. and Ran, Y. and Mahan, T. E. and Chakrabaty, P. and others},
title = {{High-affinity interactions and signal transduction between Aβ oligomers and TREM2}},
journal = {EMBO molecular medicine},
year = {2018},
doi = {10.15252/emmm.201809027},
pmid = {30341064},
url = {https://doi.org/10.15252/emmm.201809027}
}
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