Tomoyuki Ohara1,2, Jun Hata2,3,4, Masashi Tanaka5, Takanori Honda2, Hajime Yamakage5, Daigo Yoshida2,3, Takayuki Inoue5, Yoichiro Hirakawa2,4, Toru Kusakabe5, Mao Shibata2,3, Tadashi Teraoka6, Takanari Kitazono3,4, Shigenobu Kanba1, Noriko Satoh-Asahara5, Toshiharu Ninomiya2,3. 1. Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka. 2. Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka. 3. Department of Center for Cohort Studies, Graduate School of Medical Sciences, Kyushu University, Fukuoka. 4. Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka. 5. Department of Endocrinology, Metabolism, and Hypertension Research, Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto. 6. Health Science Research Institute West Japan, Kyoto, Japan.
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.
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.
Authors: Grace E Weber; Maria Khrestian; Elizabeth D Tuason; Yvonne Shao; Jagan Pillai; Stephen Rao; Hao Feng; Yadi Zhou; Feixiong Cheng; Tara M DeSilva; Shaun Stauffer; James B Leverenz; Lynn M Bekris Journal: J Immunol Date: 2022-05-06 Impact factor: 5.426
Authors: Edward N Wilson; Michelle S Swarovski; Patricia Linortner; Marian Shahid; Abigail J Zuckerman; Qian Wang; Divya Channappa; Paras S Minhas; Siddhita D Mhatre; Edward D Plowey; Joseph F Quinn; Cyrus P Zabetian; Lu Tian; Frank M Longo; Brenna Cholerton; Thomas J Montine; Kathleen L Poston; Katrin I Andreasson Journal: Brain Date: 2020-03-01 Impact factor: 13.501