Abstract
Objective: To investigate the association between serum soluble triggering receptor expressed on myeloid cells 2 (sTREM2), a soluble type of an innate immune receptor expressed on the microglia, and the risk of dementia. Methods: A total of 1,349 Japanese community residents aged 60 and older without dementia were followed prospectively for 10 years (2002–2012). Serum sTREM2 levels were quantified by using an enzyme-linked immunosorbent assay and divided into quartiles. Cox proportional hazards model was used to estimate the hazard ratios (HRs) of serum sTREM2 levels on the risk of dementia. Results: During the follow-up, 300 subjects developed all-cause dementia; 193 had Alzheimer's disease (AD), and 85 had vascular dementia (VaD). The age- and sex-adjusted incidences of all-cause dementia, AD, and VaD elevated significantly with higher serum sTREM2 levels (all p for trend < 0.012). These associations were not altered after adjustment for confounding factors, including high-sensitive C-reactive protein. Subjects with the highest quartile of serum sTREM2 levels had significantly higher multivariable-adjusted risks of developing all-cause dementia, AD, and VaD than those with the lowest quartile (HR = 2.03, 95% confidence interval [CI] = 1.39–2.97, p < 0.001 for all-cause dementia; HR = 1.62, 95% CI = 1.02–2.55, p = 0.04 for AD; HR = 2.85, 95% CI = 1.35–6.02, p = 0.006 for VaD). No significant heterogeneity in the association of serum sTREM2 levels with the development of dementia was observed among the other risk factor subgroups (all p for heterogeneity > 0.11). Interpretation: The present findings suggest a significant association between increased serum sTREM2 levels and the risk of developing all-cause dementia, AD, and VaD in the general elderly Japanese population. ANN NEUROL 2019;85:47–58.
| Original language | English |
|---|---|
| Pages (from-to) | 47-58 |
| Number of pages | 12 |
| Journal | Annals of Neurology |
| Volume | 85 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 2019 |
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All Science Journal Classification (ASJC) codes
- Neurology
- Clinical Neurology
Cite this
Serum Soluble Triggering Receptor Expressed on Myeloid Cells 2 as a Biomarker for Incident Dementia : The Hisayama Study. / Ohara, Tomoyuki; Hata, Jun; Tanaka, Masashi; Honda, Takanori; Yamakage, Hajime; Yoshida, Daigo; Inoue, Takayuki; Hirakawa, Yoichiro; Kusakabe, Toru; Shibata, Mao; Teraoka, Tadashi; Kitazono, Takanari; Kanba, Shigenobu; Satoh-Asahara, Noriko; Ninomiya, Toshiharu.
In: Annals of Neurology, Vol. 85, No. 1, 01.2019, p. 47-58.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Serum Soluble Triggering Receptor Expressed on Myeloid Cells 2 as a Biomarker for Incident Dementia
T2 - The Hisayama Study
AU - Ohara, Tomoyuki
AU - Hata, Jun
AU - Tanaka, Masashi
AU - Honda, Takanori
AU - Yamakage, Hajime
AU - Yoshida, Daigo
AU - Inoue, Takayuki
AU - Hirakawa, Yoichiro
AU - Kusakabe, Toru
AU - Shibata, Mao
AU - Teraoka, Tadashi
AU - Kitazono, Takanari
AU - Kanba, Shigenobu
AU - Satoh-Asahara, Noriko
AU - Ninomiya, Toshiharu
PY - 2019/1
Y1 - 2019/1
N2 - Objective: To investigate the association between serum soluble triggering receptor expressed on myeloid cells 2 (sTREM2), a soluble type of an innate immune receptor expressed on the microglia, and the risk of dementia. Methods: A total of 1,349 Japanese community residents aged 60 and older without dementia were followed prospectively for 10 years (2002–2012). Serum sTREM2 levels were quantified by using an enzyme-linked immunosorbent assay and divided into quartiles. Cox proportional hazards model was used to estimate the hazard ratios (HRs) of serum sTREM2 levels on the risk of dementia. Results: During the follow-up, 300 subjects developed all-cause dementia; 193 had Alzheimer's disease (AD), and 85 had vascular dementia (VaD). The age- and sex-adjusted incidences of all-cause dementia, AD, and VaD elevated significantly with higher serum sTREM2 levels (all p for trend < 0.012). These associations were not altered after adjustment for confounding factors, including high-sensitive C-reactive protein. Subjects with the highest quartile of serum sTREM2 levels had significantly higher multivariable-adjusted risks of developing all-cause dementia, AD, and VaD than those with the lowest quartile (HR = 2.03, 95% confidence interval [CI] = 1.39–2.97, p < 0.001 for all-cause dementia; HR = 1.62, 95% CI = 1.02–2.55, p = 0.04 for AD; HR = 2.85, 95% CI = 1.35–6.02, p = 0.006 for VaD). No significant heterogeneity in the association of serum sTREM2 levels with the development of dementia was observed among the other risk factor subgroups (all p for heterogeneity > 0.11). Interpretation: The present findings suggest a significant association between increased serum sTREM2 levels and the risk of developing all-cause dementia, AD, and VaD in the general elderly Japanese population. ANN NEUROL 2019;85:47–58.
AB - Objective: To investigate the association between serum soluble triggering receptor expressed on myeloid cells 2 (sTREM2), a soluble type of an innate immune receptor expressed on the microglia, and the risk of dementia. Methods: A total of 1,349 Japanese community residents aged 60 and older without dementia were followed prospectively for 10 years (2002–2012). Serum sTREM2 levels were quantified by using an enzyme-linked immunosorbent assay and divided into quartiles. Cox proportional hazards model was used to estimate the hazard ratios (HRs) of serum sTREM2 levels on the risk of dementia. Results: During the follow-up, 300 subjects developed all-cause dementia; 193 had Alzheimer's disease (AD), and 85 had vascular dementia (VaD). The age- and sex-adjusted incidences of all-cause dementia, AD, and VaD elevated significantly with higher serum sTREM2 levels (all p for trend < 0.012). These associations were not altered after adjustment for confounding factors, including high-sensitive C-reactive protein. Subjects with the highest quartile of serum sTREM2 levels had significantly higher multivariable-adjusted risks of developing all-cause dementia, AD, and VaD than those with the lowest quartile (HR = 2.03, 95% confidence interval [CI] = 1.39–2.97, p < 0.001 for all-cause dementia; HR = 1.62, 95% CI = 1.02–2.55, p = 0.04 for AD; HR = 2.85, 95% CI = 1.35–6.02, p = 0.006 for VaD). No significant heterogeneity in the association of serum sTREM2 levels with the development of dementia was observed among the other risk factor subgroups (all p for heterogeneity > 0.11). Interpretation: The present findings suggest a significant association between increased serum sTREM2 levels and the risk of developing all-cause dementia, AD, and VaD in the general elderly Japanese population. ANN NEUROL 2019;85:47–58.
UR - http://www.scopus.com/inward/record.url?scp=85059265511&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85059265511&partnerID=8YFLogxK
U2 - 10.1002/ana.25385
DO - 10.1002/ana.25385
M3 - Article
C2 - 30485483
AN - SCOPUS:85059265511
VL - 85
SP - 47
EP - 58
JO - Annals of Neurology
JF - Annals of Neurology
SN - 0364-5134
IS - 1
ER -