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TREM2 and the neuroimmunology of Alzheimer's disease
Hickman SE, El Khoury J.. Biochemical pharmacology, 2013-12-16
Topic: Amyloid, tau and blood-test diagnosis
Late-onset Alzheimer's disease (AD) is a sporadic disorder with increasing prevalence in aging. The ɛ4 allele of Apolipoprotein E(ApoEɛ4) was the only known major risk factor for late onset AD. Recently, two groups of investigators independently identified variants of the TREM2 gene, encoding triggering receptor expressed on myeloid cells 2 as causing increased susceptibility to late onset AD with an odds ratio similar to that of ApoEɛ4.
Key findings
- The ɛ4 allele of Apolipoprotein E(ApoEɛ4) was the only known major risk factor for late onset AD.
- Recently, two groups of investigators independently identified variants of the TREM2 gene, encoding triggering receptor expressed on myeloid cells 2 as causing increased susceptibility to late onset AD with an odds ratio similar to that of ApoEɛ4.
- TREM2 is a receptor expressed on innate immune cells.
- Using a novel technology called Direct RNA Sequencing wedetermined the quantitative transcriptome of microglia, the principal innate neuroimmune cells and confirmed that TREM2 is a major microglia-specific gene in the central nervous system.
Why it matters
This covers the report by two independent research groups that variants of the TREM2 gene are linked to a higher risk of late-onset Alzheimer's, with an odds ratio similar to that of APOE ε4, then the only known major genetic risk factor. TREM2 is a receptor on innate immune cells. Using Direct RNA Sequencing, the authors confirmed it is a major microglia-specific gene in the brain, which points to the brain's immune cells as part of the story. The record gives no odds-ratio figure or sample sizes, and the paper tests no treatment, so it describes a risk link, not a way to prevent or treat the disease.
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Study details
- Evidence strengthLow
How this study scored 48/100
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 (Biochemical pharmacology) |
| Journal's citation record | 3 / 4 | Biochemical Pharmacology: journal h-index 292 (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 | 2014 — within 20 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 222 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 15.9 citations a year over 14 year(s) since 2014 |
| Impact for its field and year | 3 / 6 | Cited 7.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 42 other studies in this library |
| Still being cited | 2 / 4 | Cited 43 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Joseph B. El Khoury: h-index 51 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 24355566) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 48 / 100 | — |
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Read the original
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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APA 7th
Hickman, S. E., & El Khoury, J. (2014). TREM2 and the neuroimmunology of Alzheimer's disease. Biochemical pharmacology. https://doi.org/10.1016/j.bcp.2013.11.021
Vancouver
Hickman SE, El Khoury J. TREM2 and the neuroimmunology of Alzheimer's disease. Biochemical pharmacology. 2014. doi:10.1016/j.bcp.2013.11.021. PMID: 24355566.
BibTeX
@article{hickman2014-24355566,
author = {Hickman, S. E. and El Khoury, J.},
title = {{TREM2 and the neuroimmunology of Alzheimer's disease}},
journal = {Biochemical pharmacology},
year = {2014},
doi = {10.1016/j.bcp.2013.11.021},
pmid = {24355566},
url = {https://doi.org/10.1016/j.bcp.2013.11.021}
}
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