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
N1 - Funding Information:
M.T. reports grants from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, Takeda Science Foundation, Japan Research Foundation for Clinical Pharmacology, and Kao Research Council for the Study of Healthcare Science. H.Y. reports grants from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. N.S.-A. reports grants from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, and a Satoh grant from the National Hospital Organization for collaborative clinical research. All of these may be affected by the study. The remaining authors have nothing to report.
Funding Information:
This study was supported by the Japan Agency for Medical Research and Development (JP18dk0207025, JP18ek0210082, JP18gm0610007, JP18ek0210083, JP18km0405202, JP18ek0210080, and JP18fk0108075); Health and Labor Sciences Research Grants from the Ministry of Health, Labor, and Welfare of Japan (H29-Junkankitou-Ippan-003 and H30-Shokuhin-[Sitei]-005); and Grants-in-Aid for Scientific Research (A: JP16H02644 and JP16H02692; B: JP16H05850, JP16H05557, JP17H04126, and JP18H02737; C: JP16K09244, JP17K09114, JP17K09113, JP17K01853, JP18K07565, and JP18K09412) and Grants-in-Aid for Early-Career Scientists (JP18K17925 and JP18K17382) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.
Funding Information:
This study was supported by the Japan Agency for Medical Research and Development (JP18dk0207025, JP18ek0210082, JP18gm0610007, JP18ek0210083, JP18km0405202, JP18ek0210080, and JP18fk0108075); Health and Labor Sciences Research Grants from the Ministry of Health, Labor, and Welfare of Japan (H29-Junkankitou-Ippan-003 and H30-Shokuhin-[Sitei]-005); and Grants-in-Aid for Scientific Research (A: JP16H02644 and JP16H02692; B: JP16H05850, JP16H05557, JP17H04126, and JP18H02737; C: JP16K09244, JP17K09114, JP17K09113, JP17K01853, JP18K07565, and JP18K09412) and Grants-in-Aid for Early-Career Scientists (JP18K17925 and JP18K17382) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. We thank the Hisayama residents for their participation in the survey; the staff of the Division of Health and Welfare of Hisayama for their cooperation with this study; and Dr T. Iwaki, Dr Y. Oda, and their colleagues at the Department of Neuropathology and Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, who provided crucial insight into the autopsy findings. T.O. and T.N. performed the statistical analysis at the Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. No study sponsors had any role in the study design, data collection, study data interpretation, or preparation of the manuscript.
Publisher Copyright:
© 2018 American Neurological Association
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.
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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 -