Serum Soluble Triggering Receptor Expressed on Myeloid Cells 2 as a Biomarker for Incident Dementia: The Hisayama Study

被引:51
作者
Ohara, Tomoyuki [1 ,2 ]
Hata, Jun [2 ,3 ,4 ]
Tanaka, Masashi [5 ]
Honda, Takanori [2 ]
Yamakage, Hajime [5 ]
Yoshida, Daigo [2 ,3 ]
Inoue, Takayuki [5 ]
Hirakawa, Yoichiro [2 ,4 ]
Kusakabe, Toru [5 ]
Shibata, Mao [2 ,3 ]
Teraoka, Tadashi [6 ]
Kitazono, Takanari [3 ,4 ]
Kanba, Shigenobu [1 ]
Satoh-Asahara, Noriko [5 ]
Ninomiya, Toshiharu [2 ,3 ]
机构
[1] Kyushu Univ, Grad Sch Med Sci, Dept Neuropsychiat, Fukuoka, Fukuoka, Japan
[2] Kyushu Univ, Grad Sch Med Sci, Dept Epidemiol & Publ Hlth, Fukuoka, Fukuoka, Japan
[3] Kyushu Univ, Grad Sch Med Sci, Dept Ctr Cohort Studies, Fukuoka, Fukuoka, Japan
[4] Kyushu Univ, Grad Sch Med Sci, Dept Med & Clin Sci, Fukuoka, Fukuoka, Japan
[5] Natl Hosp Org Kyoto Med Ctr, Dept Endocrinol Metab & Hypertens Res, Clin Res Inst, Kyoto, Japan
[6] Hlth Sci Res Inst West Japan, Kyoto, Japan
关键词
CEREBROSPINAL-FLUID; ALZHEIMERS-DISEASE; TREM2; DEFICIENCY; MULTIPLE-SCLEROSIS; MICROGLIA; RISK; IMPAIRS; INFLAMMATION; POPULATION; COMMUNITY;
D O I
10.1002/ana.25385
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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.
引用
收藏
页码:47 / 58
页数:12
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