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Multimerization of TREM2 is impaired by Alzheimer's disease-associated variants
Hunter B Dean, Rory A Greer, Shan-Zhong Yang, Daniel S Elston, Thomas J Brett, Erik D Roberson, Yuhua Song. Alzheimer's & dementia : the journal of the Alzheimer's Association, 2024-07-20
Topic: Disease mechanisms in lab and animal studies
TREM2 trimers remained stably bound, driven primarily by salt bridge between residues D87 and R76 at the interface of TREM2 units. This salt bridge was disrupted by the AD-associated variants R47H and R98W and nearly ablated by the D87N variant. This decreased binding among TREM2 multimers was validated with co-immunoprecipitation assays. This study uncovers a molecular basis for TREM2 forming stable trimers and unveils a novel mechanism by which TREM2 variants may increase AD risk by disrupting TREM2 oligomerization to impair TREM2 normal function. HIGHLIGHTS: Triggering receptor expressed on myeloid cells 2 (TREM2) multimerization could regulate TREM2 activation and function. D87-R76 salt bridges at the interface of TREM2 units drive the formation of stable TREM2 dimers and trimers. Alzheimer's disease (AD)-associated R47H and R98W variants disrupt the D87-R76 salt bridge. The AD-associated D87N variant leads to complete loss of the D87-R76 salt bridge.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Dean, H. B., Greer, R. A., Yang, S.-Z., Elston, D. S., Brett, T. J., Roberson, E. D., et al. (2024). Multimerization of TREM2 is impaired by Alzheimer's disease-associated variants. Alzheimer's & dementia : the journal of the Alzheimer's Association. https://doi.org/10.1002/alz.14124
Vancouver
Dean HB, Greer RA, Yang S.-Z, Elston DS, Brett TJ, Roberson ED, et al. Multimerization of TREM2 is impaired by Alzheimer's disease-associated variants. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2024. doi:10.1002/alz.14124. PMID: 39032157.
BibTeX
@article{dean2024-39032157,
author = {Dean, Hunter B and Greer, Rory A and Yang, Shan-Zhong and Elston, Daniel S and Brett, Thomas J and Roberson, Erik D and Song, Yuhua},
title = {{Multimerization of TREM2 is impaired by Alzheimer's disease-associated variants}},
journal = {Alzheimer's \& dementia : the journal of the Alzheimer's Association},
year = {2024},
doi = {10.1002/alz.14124},
pmid = {39032157},
url = {https://doi.org/10.1002/alz.14124}
}
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 7 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.
Key findings
- TREM2 trimers remained stably bound, driven primarily by salt bridge between residues D87 and R76 at the interface of TREM2 units.
- This salt bridge was disrupted by the AD-associated variants R47H and R98W and nearly ablated by the D87N variant.
- This decreased binding among TREM2 multimers was validated with co-immunoprecipitation assays.
- This study uncovers a molecular basis for TREM2 forming stable trimers and unveils a novel mechanism by which TREM2 variants may increase AD risk by disrupting TREM2 oligomerization to impair TREM2 normal function.
- HIGHLIGHTS: Triggering receptor expressed on myeloid cells 2 (TREM2) multimerization could regulate TREM2 activation and function.
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Study details
- Evidence strengthLow
How this study scored 46/100
Published in a leading specialty journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / 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, multicenter collaboration and free to read, so those were left out: it earned 26 of the 56 points we could judge it on, which is 46 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Alzheimer's & dementia : the journal of the Alzheimer's Association) |
| 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 | 4 / 5 | 2024 — within 3 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) |
| Randomized / blinded | 0 / 2 | No randomization 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 |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 39032157) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 26 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 26 of the 56 points we could judge it on is 46 out of 100. |
| Total | 46 / 100 | — |
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