| Title |
Cerebrospinal fluid soluble TREM2 is higher in Alzheimer disease and associated with mutation status
|
|---|---|
| Published in |
Acta Neuropathologica, January 2016
|
| DOI | 10.1007/s00401-016-1533-5 |
| Pubmed ID | |
| Authors |
Laura Piccio, Yuetiva Deming, Jorge L. Del-Águila, Laura Ghezzi, David M. Holtzman, Anne M. Fagan, Chiara Fenoglio, Daniela Galimberti, Barbara Borroni, Carlos Cruchaga |
| Abstract |
Low frequency coding variants in TREM2 are associated with increased Alzheimer disease (AD) risk, while loss of functions mutations in the gene lead to an autosomal recessive early-onset dementia, named Nasu-Hakola disease (NHD). TREM2 can be detected as a soluble protein in cerebrospinal fluid (CSF) and plasma, and its CSF levels are elevated in inflammatory CNS diseases. We measured soluble TREM2 (sTREM2) in the CSF of a large AD case-control dataset (n = 180) and 40 TREM2 risk variant carriers to determine whether CSF sTREM2 levels are associated with AD status or mutation status. We also performed genetic studies to identify genetic variants associated with CSF sTREM2 levels. CSF, but not plasma, sTREM2 was highly correlated with CSF total tau and phosphorylated-tau levels (r = 0.35, P < 1×10(-4); r = 0.40, P < 1×10(-4), respectively), but not with CSF Aβ42. AD cases presented higher CSF sTREM2 levels than controls (P = 0.01). Carriers of NHD-associated TREM2 variants presented significantly lower CSF sTREM2 levels, supporting the hypothesis that these mutations lead to reduced protein production/function (R136Q, D87N, Q33X or T66M; P = 1×10(-3)). In contrast, CSF sTREM2 levels were significantly higher in R47H carriers compared to non-carriers (P = 6×10(-3)), suggesting that this variant does not impact protein expression and increases AD risk through a different pathogenic mechanism than NHD variants. In GWAS analyses for CSF sTREM2 levels the most significant signal was located on the MS4A gene locus (P = 5.45 × 10(-07)) corresponding to one of the SNPs reported to be associated with AD risk in this locus. Furthermore, SNPs involved in pathways related to virus cellular entry and vesicular trafficking were overrepresented, suggesting that CSF sTREM2 levels could be an informative phenotype for AD. |
X Demographics
The data shown below were collected from the profiles of 6 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 2 | 33% |
| Spain | 1 | 17% |
| Denmark | 1 | 17% |
| Unknown | 2 | 33% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 4 | 67% |
| Practitioners (doctors, other healthcare professionals) | 1 | 17% |
| Scientists | 1 | 17% |
Mendeley readers
The data shown below were compiled from readership statistics for 298 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 298 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 51 | 17% |
| Student > Ph. D. Student | 48 | 16% |
| Student > Master | 26 | 9% |
| Student > Bachelor | 25 | 8% |
| Student > Doctoral Student | 9 | 3% |
| Other | 42 | 14% |
| Unknown | 97 | 33% |
| Readers by discipline | Count | As % |
|---|---|---|
| Neuroscience | 69 | 23% |
| Medicine and Dentistry | 34 | 11% |
| Agricultural and Biological Sciences | 27 | 9% |
| Biochemistry, Genetics and Molecular Biology | 23 | 8% |
| Pharmacology, Toxicology and Pharmaceutical Science | 11 | 4% |
| Other | 34 | 11% |
| Unknown | 100 | 34% |
Attention Score in Context
This research output has an Altmetric Attention Score of 22. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 15 August 2023.
All research outputs
#1,492,845
of 23,543,207 outputs
Outputs from Acta Neuropathologica
#277
of 2,409 outputs
Outputs of similar age
#27,596
of 398,264 outputs
Outputs of similar age from Acta Neuropathologica
#6
of 39 outputs
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