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The triggering receptor expressed on myeloid cells 2 (TREM2) is associated with enhanced inflammation, neuropathological lesions and increased risk for Alzheimer's dementia
Roussos P, Katsel P, Fam P, Tan W, Purohit DP, Haroutunian V.. Alzheimer's & dementia : the journal of the Alzheimer's Association, 2014-12-09
Topic: Brain proteins, microglia and lab models
Introduction The objective of this study was to elucidate the relationship between the triggering receptor expressed on myeloid cells 2 (TREM2) risk variant, neuropathological lesions, alterations in gene and protein expression, and the severity of neuroinflammation. Methods The genetic association study of the R47 H TREM2 variant with Alzheimer's disease (AD), neuropathology, and changes in TREM2 and TYRO protein tyrosine kinase-binding protein (TYROBP) gene and protein expression, and neuroinflammatory markers. Results The TREM2 variant is associated with: (i) AD (odds ratio: 4.76; P = .014); (ii) increased density of amyloid plaques and neurofibrillary tangles in multiple brain regions; (iii) increased TREM2 (P = .041) and TYROBP (P = .006) gene expression; (iv) decreased TREM2 protein levels (P = .016); and (v) upregulation of proinflammatory cytokines (regulated on activation, norma
Key findings
- Methods The genetic association study of the R47 H TREM2 variant with Alzheimer's disease (AD), neuropathology, and changes in TREM2 and TYRO protein tyrosine kinase-binding protein (TYROBP) gene and protein expression, and neuroinflammatory markers.
- Results The TREM2 variant is associated with: (i) AD (odds ratio: 4.76; P = .014); (ii) increased density of amyloid plaques and neurofibrillary tangles in multiple brain regions; (iii) increased TREM2 (P = .041) and TYROBP (P = .006) gene expression; (iv) decreased TREM2 protein levels (P = .016); and (v) upregulation of proinflammatory cytokines (regulated on activation, normal T cell expressed and secreted [RANTES] and interferon [IFN] gamma) (P = .003) and nominal downregulation of protective markers (α2-macroglobulin, interleukin 4 or IL-4, and ApoA1) (P = .018).
- Discussion These findings link the TREM2 missense mutation with specific molecular abnormalities and increases in neuropathological lesions in the human brain.
Why it matters
The TREM2 R47H variant was associated with higher odds of Alzheimer's dementia, more amyloid plaques and neurofibrillary tangles, and signs of increased inflammation in brain tissue. This links the variant to more severe disease features, but it is an association study and does not test any treatment.
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Study details
- Evidence strengthLow
How this study scored 45/100
Published in a leading specialty 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 | 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 | 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 | 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 101 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 7.8 citations a year over 13 year(s) since 2015 |
| Impact for its field and year | 2 / 6 | Cited 2.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 26 other studies in this library |
| Still being cited | 2 / 4 | Cited 24 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Vahram H. Haroutunian: h-index 107 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Icahn School of Medicine at Mount Sinai: institution h-index 1,331 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 25499537) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 45 / 100 | — |
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APA 7th
Roussos, P., Katsel, P., Fam, P., Tan, W., Purohit, D. P., & Haroutunian, V. (2015). The triggering receptor expressed on myeloid cells 2 (TREM2) is associated with enhanced inflammation, neuropathological lesions and increased risk for Alzheimer's dementia. Alzheimer's & dementia : the journal of the Alzheimer's Association. https://doi.org/10.1016/j.jalz.2014.10.013
Vancouver
Roussos P, Katsel P, Fam P, Tan W, Purohit DP, Haroutunian V. The triggering receptor expressed on myeloid cells 2 (TREM2) is associated with enhanced inflammation, neuropathological lesions and increased risk for Alzheimer's dementia. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2015. doi:10.1016/j.jalz.2014.10.013. PMID: 25499537.
BibTeX
@article{roussos2015-25499537,
author = {Roussos, P. and Katsel, P. and Fam, P. and Tan, W. and Purohit, D. P. and Haroutunian, V.},
title = {{The triggering receptor expressed on myeloid cells 2 (TREM2) is associated with enhanced inflammation, neuropathological lesions and increased risk for Alzheimer's dementia}},
journal = {Alzheimer's \& dementia : the journal of the Alzheimer's Association},
year = {2015},
doi = {10.1016/j.jalz.2014.10.013},
pmid = {25499537},
url = {https://doi.org/10.1016/j.jalz.2014.10.013}
}
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