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Increased soluble TREM2 in cerebrospinal fluid is associated with reduced cognitive and clinical decline in Alzheimer's disease
Ewers M, Franzmeier N, Suárez-Calvet M, Morenas-Rodriguez E, Caballero MAA, Kleinberger G, Piccio L, Cruchaga C et al.. Science translational medicine, 2019-08-01
Topic: Brain proteins, microglia and lab models
Loss of function of TREM2, a key receptor selectively expressed by microglia in the brain, contributes to the development of Alzheimer's disease (AD). We therefore examined whether soluble TREM2 (sTREM2) concentrations in cerebrospinal fluid (CSF) were associated with reduced rates of cognitive decline and clinical progression in subjects with AD or mild cognitive impairment (MCI). We measured sTREM2 in CSF samples from 385 elderly subjects, including cognitively normal controls, individuals with MCI, and subjects with AD dementia (follow-up period: mean, 4 years; range 1.5 to 11.5 years). In subjects with AD defined by evidence of CSF Aβ 1-42 (amyloid β-peptide 1 to 42; A+) and CSF p-tau 181 (tau phosphorylated on amino acid residue 181; T+), higher sTREM2 concentrations in CSF at baseline were associated with attenuated decline in memory and cognition. When analyzed in clinical subgroups, an association between higher CSF sTREM2 concentrations and subsequent reduced memory decline was consistently observed in individuals with MCI or AD dementia, who were positive for CSF Aβ 1-42 and CSF p-tau 181 (A+T+). Regarding clinical progression, a higher ratio of CSF sTREM2 to CSF p-tau 181 concentrations predicted slower conversion from cognitively normal to symptomatic stages or from MCI to AD dementia in the subjects who were positive for CSF Aβ 1-42 and CSF p-tau 181. These results suggest that sTREM2 is associated with attenuated cognitive and clinical decline, a finding with important implications for future clinical trials targeting the innate immune response in AD.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Ewers, M., Franzmeier, N., Suárez-Calvet, M., Morenas-Rodriguez, E., Caballero, M. A. A., Kleinberger, G., et al. (2019). Increased soluble TREM2 in cerebrospinal fluid is associated with reduced cognitive and clinical decline in Alzheimer's disease. Science translational medicine. https://doi.org/10.1126/scitranslmed.aav6221
Vancouver
Ewers M, Franzmeier N, Suárez-Calvet M, Morenas-Rodriguez E, Caballero MAA, Kleinberger G, et al. Increased soluble TREM2 in cerebrospinal fluid is associated with reduced cognitive and clinical decline in Alzheimer's disease. Science translational medicine. 2019. doi:10.1126/scitranslmed.aav6221. PMID: 31462511.
BibTeX
@article{ewers2019-31462511,
author = {Ewers, M. and Franzmeier, N. and Suárez-Calvet, M. and Morenas-Rodriguez, E. and Caballero, M. A. A. and Kleinberger, G. and Piccio, L. and Cruchaga, C. and others},
title = {{Increased soluble TREM2 in cerebrospinal fluid is associated with reduced cognitive and clinical decline in Alzheimer's disease}},
journal = {Science translational medicine},
year = {2019},
doi = {10.1126/scitranslmed.aav6221},
pmid = {31462511},
url = {https://doi.org/10.1126/scitranslmed.aav6221}
}
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
- We therefore examined whether soluble TREM2 (sTREM2) concentrations in cerebrospinal fluid (CSF) were associated with reduced rates of cognitive decline and clinical progression in subjects with AD or mild cognitive impairment (MCI).
- In subjects with AD defined by evidence of CSF Aβ 1-42 (amyloid β-peptide 1 to 42; A+) and CSF p-tau 181 (tau phosphorylated on amino acid residue 181; T+), higher sTREM2 concentrations in CSF at baseline were associated with attenuated decline in memory and cognition.
- These results suggest that sTREM2 is associated with attenuated cognitive and clinical decline, a finding with important implications for future clinical trials targeting the innate immune response in AD.
Why it matters
In 385 elderly subjects followed for a mean of 4 years, higher cerebrospinal fluid soluble TREM2 at baseline was associated with slower memory and cognitive decline in those positive for amyloid and tau markers, and a higher sTREM2-to-p-tau181 ratio predicted slower progression to dementia. This suggests sTREM2 could be a marker of slower decline, but it does not show that raising it treats or cures Alzheimer's disease.
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. We have no data on senior author's track record, so that was left out: it earned 51 of the 96 points we could judge it on, which is 53 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Science translational medicine) |
| Journal's citation record | 3 / 4 | Science Translational Medicine: journal h-index 365 (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 | 2019 — 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 | 6 / 7 | Cited 323 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 35.9 citations a year over 9 year(s) since 2019 |
| Impact for its field and year | 4 / 6 | Cited 13.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 49 other studies in this library |
| Still being cited | 3 / 4 | Cited 138 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | 2 / 3 | Washington University in St. Louis: institution h-index 1,962 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 15 institution(s) in 4 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 31462511) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 51 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 51 of the 96 points we could judge it on is 53 out of 100. |
| Total | 53 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1126/scitranslmed.aav6221
- PubMed: 31462511
- Original source →
- Free full text: eScholarship (California Digital Library) →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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