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The Trem2 R47H variant confers loss-of-function-like phenotypes in Alzheimer's disease
Cheng-Hathaway PJ, Reed-Geaghan EG, Jay TR, Casali BT, Bemiller SM, Puntambekar SS, von Saucken VE, Williams RY et al.. Molecular neurodegeneration, 2018-06-01
Topic: Brain proteins, microglia and lab models
Background The R47H variant of Triggering Receptor Expressed on Myeloid cells 2 (TREM2) confers greatly increased risk for Alzheimer's disease (AD), reflective of a central role for myeloid cells in neurodegeneration. Understanding how this variant confers AD risk promises to provide important insights into how myeloid cells contribute to AD pathogenesis and progression. Methods In order to investigate this mechanism, CRISPR/Cas9 was used to generate a mouse model of AD harboring one copy of the single nucleotide polymorphism (SNP) encoding the R47H variant in murine Trem2.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Cheng-Hathaway, P. J., Reed-Geaghan, E. G., Jay, T. R., Casali, B. T., Bemiller, S. M., Puntambekar, S. S., et al. (2018). The Trem2 R47H variant confers loss-of-function-like phenotypes in Alzheimer's disease. Molecular neurodegeneration. https://doi.org/10.1186/s13024-018-0262-8
Vancouver
Cheng-Hathaway PJ, Reed-Geaghan EG, Jay TR, Casali BT, Bemiller SM, Puntambekar SS, et al. The Trem2 R47H variant confers loss-of-function-like phenotypes in Alzheimer's disease. Molecular neurodegeneration. 2018. doi:10.1186/s13024-018-0262-8. PMID: 29859094.
BibTeX
@article{chenghathaway2018-29859094,
author = {Cheng-Hathaway, P. J. and Reed-Geaghan, E. G. and Jay, T. R. and Casali, B. T. and Bemiller, S. M. and Puntambekar, S. S. and von Saucken, V. E. and Williams, R. Y. and others},
title = {{The Trem2 R47H variant confers loss-of-function-like phenotypes in Alzheimer's disease}},
journal = {Molecular neurodegeneration},
year = {2018},
doi = {10.1186/s13024-018-0262-8},
pmid = {29859094},
url = {https://doi.org/10.1186/s13024-018-0262-8}
}
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.
Key findings
- Understanding how this variant confers AD risk promises to provide important insights into how myeloid cells contribute to AD pathogenesis and progression.
- Methods In order to investigate this mechanism, CRISPR/Cas9 was used to generate a mouse model of AD harboring one copy of the single nucleotide polymorphism (SNP) encoding the R47H variant in murine Trem2.
- TREM2 expression, myeloid cell responses to amyloid deposition, plaque burden, and neuritic dystrophy were assessed at 4 months of age.
- Results AD mice heterozygous for the Trem2 R47H allele exhibited reduced total Trem2 mRNA expression, reduced TREM2 expression around plaques, and reduced association of myeloid cells with plaques.
Why it matters
In mice engineered to carry one copy of the TREM2 R47H variant, a variant the authors describe as conferring "greatly increased risk" for Alzheimer's disease, the researchers report lower Trem2 mRNA, less TREM2 around amyloid plaques, and fewer immune (myeloid) cells gathered around plaques at 4 months of age. The authors describe these as "loss-of-function-like" effects; the record does not report what was found for plaque burden or nerve-fibre damage. This is a mouse study, it does not show how the variant behaves in people, and it tested no treatment.
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Study details
- Evidence strengthLow
How this study scored 53/100
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 (Molecular neurodegeneration) |
| Journal's citation record | 2 / 4 | Molecular Neurodegeneration: journal h-index 164 (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 252 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 25.2 citations a year over 10 year(s) since 2018 |
| Impact for its field and year | 4 / 6 | Cited 17.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 48 other studies in this library |
| Still being cited | 3 / 4 | Cited 75 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Gary E. Landreth: h-index 101 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Case Western Reserve University: institution h-index 1,159 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 6 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 29859094) |
| Free to read | 2 / 2 | Free to read |
| Total | 53 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1186/s13024-018-0262-8
- PubMed: 29859094
- Original source →
- Free full text: Molecular Neurodegeneration →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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