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The role of TREM2 R47H as a risk factor for Alzheimer's disease, frontotemporal lobar degeneration, amyotrophic lateral sclerosis, and Parkinson's disease
Lill CM, Rengmark A, Pihlstrøm L, Fogh I, Shatunov A, Sleiman PM, Wang LS, Liu T et al.. Alzheimer's & dementia : the journal of the Alzheimer's Association, 2015-04-30
Topic: Brain proteins, microglia and lab models
A rare variant in TREM2 (p.R47H, rs75932628) was recently reported to increase the risk of Alzheimer's disease (AD) and, subsequently, other neurodegenerative diseases, i.e. frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). Here we comprehensively assessed TREM2 rs75932628 for association with these diseases in a total of 19,940 previously untyped subjects of European descent. These data were combined with those from 28 published data sets by meta-analysis.
Key findings
- Here we comprehensively assessed TREM2 rs75932628 for association with these diseases in a total of 19,940 previously untyped subjects of European descent.
- These data were combined with those from 28 published data sets by meta-analysis.
- Furthermore, we tested whether rs75932628 shows association with amyloid beta (Aβ42) and total-tau protein levels in the cerebrospinal fluid (CSF) of 828 individuals with AD or mild cognitive impairment.
- Our data show that rs75932628 is highly significantly associated with the risk of AD across 24,086 AD cases and 148,993 controls of European descent (odds ratio or OR = 2.71, P = 4.67 × 10(-25)).
Why it matters
This study tested a rare change in the TREM2 gene, called R47H, in 19,940 new people of European descent and pooled them with 28 earlier data sets. Across 24,086 people with Alzheimer's disease and 148,993 without, carriers had about 2.7 times the odds of having Alzheimer's (odds ratio 2.71). The study also looked at three other brain diseases and at amyloid and tau in spinal fluid, but those results are not in our record; it shows a genetic association in European-descent samples, not a cause, and reports no treatment or prevention.
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Study details
- Study designmeta-analysis
- Participants828
- Effect sizeOR = 2.71; OR = 2.24; OR = 1.36
- Evidence strengthHigh
How this study scored 75/100
Published in a leading specialty journal, and it is a meta-analysis pooling many studies.
| 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 | 2 / 4 | Alzheimer s & Dementia: journal h-index 228 (OpenAlex, 2026-10-29) |
| Study design | 12 / 12 | A meta-analysis pooling many studies |
| Strength of evidence | 5 / 5 | Rated “high” 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 | 828 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | A review of other studies — randomisation is not credited here |
| Times cited | 5 / 7 | Cited 205 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 15.8 citations a year over 13 year(s) since 2015 |
| Impact for its field and year | 4 / 6 | Cited 17.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 44 other studies in this library |
| Still being cited | 2 / 4 | Cited 31 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Lars Bertram: h-index 77 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of California, Los Angeles: institution h-index 1,923 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 39 institution(s) in 9 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 25936935) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 75 / 100 | — |
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Read the original
- DOI: 10.1016/j.jalz.2014.12.009
- PubMed: 25936935
- Original source →
- Free full text: Alzheimer s & Dementia →
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
Lill, C. M., Rengmark, A., Pihlstrøm, L., Fogh, I., Shatunov, A., Sleiman, P. M., et al. (2015). The role of TREM2 R47H as a risk factor for Alzheimer's disease, frontotemporal lobar degeneration, amyotrophic lateral sclerosis, and Parkinson's disease. Alzheimer's & dementia : the journal of the Alzheimer's Association. https://doi.org/10.1016/j.jalz.2014.12.009
Vancouver
Lill CM, Rengmark A, Pihlstrøm L, Fogh I, Shatunov A, Sleiman PM, et al. The role of TREM2 R47H as a risk factor for Alzheimer's disease, frontotemporal lobar degeneration, amyotrophic lateral sclerosis, and Parkinson's disease. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2015. doi:10.1016/j.jalz.2014.12.009. PMID: 25936935.
BibTeX
@article{lill2015-25936935,
author = {Lill, C. M. and Rengmark, A. and Pihlstrøm, L. and Fogh, I. and Shatunov, A. and Sleiman, P. M. and Wang, L. S. and Liu, T. and others},
title = {{The role of TREM2 R47H as a risk factor for Alzheimer's disease, frontotemporal lobar degeneration, amyotrophic lateral sclerosis, and Parkinson's disease}},
journal = {Alzheimer's \& dementia : the journal of the Alzheimer's Association},
year = {2015},
doi = {10.1016/j.jalz.2014.12.009},
pmid = {25936935},
url = {https://doi.org/10.1016/j.jalz.2014.12.009}
}
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