Serum Soluble Triggering Receptor Expressed on Myeloid Cells 2 as a Biomarker for Incident Dementia

The Hisayama Study

Tomoyuki Ohara, Jun Hata, Masashi Tanaka, Takanori Honda, Hajime Yamakage, Daigo Yoshida, Takayuki Inoue, Yoichiro Hirakawa, Toru Kusakabe, Mao Shibata, Tadashi Teraoka, Takanari Kitazono, Shigenobu Kanba, Noriko Satoh-Asahara, Toshiharu Ninomiya

Research output: Contribution to journalArticle

1 Citation (Scopus)

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 languageEnglish
Pages (from-to)47-58
Number of pages12
JournalAnnals of Neurology
Volume85
Issue number1
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Myeloid Cells
Dementia
Biomarkers
Alzheimer Disease
Vascular Dementia
Serum
Microglia
Proportional Hazards Models
Enzyme-Linked Immunosorbent Assay
Incidence
Population

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, 01.01.2019, p. 47-58.

Research output: Contribution to journalArticle

@article{7c36db90c8044955a8a658eeb4e7eb94,
title = "Serum Soluble Triggering Receptor Expressed on Myeloid Cells 2 as a Biomarker for Incident Dementia: The Hisayama Study",
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.",
author = "Tomoyuki Ohara and Jun Hata and Masashi Tanaka and Takanori Honda and Hajime Yamakage and Daigo Yoshida and Takayuki Inoue and Yoichiro Hirakawa and Toru Kusakabe and Mao Shibata and Tadashi Teraoka and Takanari Kitazono and Shigenobu Kanba and Noriko Satoh-Asahara and Toshiharu Ninomiya",
year = "2019",
month = "1",
day = "1",
doi = "10.1002/ana.25385",
language = "English",
volume = "85",
pages = "47--58",
journal = "Annals of Neurology",
issn = "0364-5134",
publisher = "John Wiley and Sons Inc.",
number = "1",

}

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 - 2019/1/1

Y1 - 2019/1/1

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

VL - 85

SP - 47

EP - 58

JO - Annals of Neurology

JF - Annals of Neurology

SN - 0364-5134

IS - 1

ER -