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CD33 modulates TREM2: convergence of Alzheimer loci
Chan G, White CC, Winn PA, Cimpean M, Replogle JM, Glick LR, Cuerdon NE, Ryan KJ et al.. Nature neuroscience, 2015-09-28
Topic: Brain proteins, microglia and lab models
We used a protein quantitative trait analysis in monocytes from 226 individuals to evaluate cross-talk between Alzheimer loci. The NME8 locus influenced PTK2B and the CD33 risk allele led to greater TREM2 expression. There was also a decreased TREM1/TREM2 ratio with a TREM1 risk allele, decreased TREM2 expression with CD33 suppression and elevated cortical TREM2 mRNA expression with amyloid pathology.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Chan, G., White, C. C., Winn, P. A., Cimpean, M., Replogle, J. M., Glick, L. R., et al. (2015). CD33 modulates TREM2: convergence of Alzheimer loci. Nature neuroscience. https://doi.org/10.1038/nn.4126
Vancouver
Chan G, White CC, Winn PA, Cimpean M, Replogle JM, Glick LR, et al. CD33 modulates TREM2: convergence of Alzheimer loci. Nature neuroscience. 2015. doi:10.1038/nn.4126. PMID: 26414614.
BibTeX
@article{chan2015-26414614,
author = {Chan, G. and White, C. C. and Winn, P. A. and Cimpean, M. and Replogle, J. M. and Glick, L. R. and Cuerdon, N. E. and Ryan, K. J. and others},
title = {{CD33 modulates TREM2: convergence of Alzheimer loci}},
journal = {Nature neuroscience},
year = {2015},
doi = {10.1038/nn.4126},
pmid = {26414614},
url = {https://doi.org/10.1038/nn.4126}
}
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Key findings
- The NME8 locus influenced PTK2B and the CD33 risk allele led to greater TREM2 expression.
- There was also a decreased TREM1/TREM2 ratio with a TREM1 risk allele, decreased TREM2 expression with CD33 suppression and elevated cortical TREM2 mRNA expression with amyloid pathology.
Why it matters
In immune cells (monocytes) taken from the blood of 226 people, this study found that carrying the CD33 Alzheimer risk allele went with greater TREM2 expression, and that suppressing CD33 lowered TREM2. It also reported that the NME8 locus influenced PTK2B, and that cortical TREM2 mRNA was higher with amyloid pathology. These findings link several Alzheimer risk genes to one another, but the study tests no treatment and reports no effect on memory, diagnosis or disease progression.
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Study details
- Participants226
- Evidence strengthLow
How this study scored 60/100
Published in a leading specialty journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Nature neuroscience) |
| Journal's citation record | 4 / 4 | Nature Neuroscience: journal h-index 593 (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 | 1 / 5 | 2015 — within 20 year(s) of the newest study here |
| Sample size | 2 / 4 | 226 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 162 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 12.5 citations a year over 13 year(s) since 2015 |
| Impact for its field and year | 4 / 6 | Cited 13.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 22 other studies in this library |
| Still being cited | 2 / 4 | Cited 35 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Philip L. De Jager: h-index 143 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 26414614) |
| Free to read | 2 / 2 | Free to read |
| Total | 60 / 100 | — |
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