TREM2作为阿尔茨海默病潜在生物学标志物的研究

发布时间：2018-01-03 14:27

本文关键词：TREM2作为阿尔茨海默病潜在生物学标志物的研究　出处：《青岛大学》2014年硕士论文　论文类型：学位论文

【摘要】：目的：本研究旨在探讨髓样细胞2触发受体(TREM2)作为阿尔茨海默病(AD)诊断生物学标志的潜在价值。方法：采用病例对照研究,选取年龄和性别相匹配的北方汉族人群的116例散发阿尔茨海默病患者和116例健康人为研究对象。应用实时荧光定量(RT-PCR)检测外周血单个核细胞(单核细胞和淋巴细胞)中TREM2mRNA水平,应用流式细胞仪(FCM)和酶联免疫实验(ELISA)对外周血细胞和血浆中TREM2蛋白水平的表达差异进行研究；应用参数检验等统计学方法进行分析；应用受试者工作特征曲线(ROC)对TREM2作为AD诊断的特异性和灵敏度进行分析。结果：TREM2mRNA在AD患者和健康对照组外周血单个核细胞(PBMCs)中表达水平差异有统计学意义：AD组/对照组：0.69±0.25/0.60±0.17,p=0.002；TREM2蛋白在单核细胞上表达水平差异有统计学意义：AD组/对照组：41.28±15.72%/27.00±15.28%,p0.001；TREM2蛋白在中性粒细胞和血浆中在AD组中的表达较健康对照组高(38.36±21.33%versus34.56±20.19%,p=0.19：20.97±7.25ng/Lversus19.63±6.84ng/L,p=0.154),虽然这种差异未达到统计学意义；此外,我们发现TREM2在淋巴细胞上不表达。在AD组中,TREM2mRNA水平与简易精神状态量表(MMSE)评分之间存在显著的相关性(r=-0.482,p0.01),TREM2蛋白水平与MMSE评分之间亦存在显著相关性(r=-0.582,p0.01)；采用ROC曲线对TREM2mRNA水平进行分析,TREM2mRNA的曲线下面积为0.596,其在AD诊断中灵敏度和特异度分别为56%、55%；采用ROC曲线对AD组和对照组单核细胞上TREM2蛋白表达水平差异进行分析,TREM2在AD诊断中的敏感度和特异度为68%和72%,诊断准确率为70%。结论：研究发现TREM2在AD患者PBMCs中mRNA及蛋白的表达水平均较健康人表达升高,虽然,TREM2不能作为独立的AD的生物学标记,但联合其他指标能提高TREM2的诊断价值。
[Abstract]:Objective: to investigate the potential value of myeloid cell 2 trigger receptor (TREM2) as a diagnostic marker for Alzheimer's disease (AD). Methods: a case-control study was conducted. A total of 116 sporadic Alzheimer's disease patients and 116 healthy persons were selected from Han nationality population of northern China matched by age and sex. Real-time fluorescence quantitative analysis (RT-PCR) was used. The levels of TREM2mRNA in peripheral blood mononuclear cells (monocytes and lymphocytes) were measured. Flow cytometry (FCM) and enzyme-linked immunosorbent assay (Elisa) were used to study the expression of TREM2 protein in peripheral blood cells and plasma. Statistical methods such as parameter test were used to analyze; The specificity and sensitivity of TREM2 in the diagnosis of AD were analyzed by using the operating characteristic curve of subjects. Results the expression of TREM2 mRNA in PBMCsof peripheral blood mononuclear cells (PBMC) in AD patients and healthy controls. There was significant difference in the expression level between the two groups. The ratio of the two groups was 0.69 卤0.25 / 0.60 卤0.17. P0. 002; The expression level of TREM2 protein in monocytes was significantly different from that in the control group and the control group: 41.28 卤15.72% / 27.00 卤15.28p 0.001; The expression of TREM2 protein in neutrophils and plasma was 38.36 卤21.33 in AD group and 34.56 卤20.19% in control group. P: 0.1920.97 卤7.25ng / L versus 19.63 卤6.84ng / L = 0.154ng / L, although the difference was not statistically significant; In addition, we found that TREM2 was not expressed on lymphocytes. There was a significant correlation between TREM2mRNA level and MMSE score. There was also a significant correlation between TREM2 protein level and MMSE score. The area under the curve of TREM2mRNA level analysis by ROC curve was 0.596. The sensitivity and specificity of TREM2 in AD diagnosis were 56%, respectively. 55. The difference of TREM2 protein expression between AD group and control group was analyzed by ROC curve. The sensitivity and specificity of TREM2 in AD diagnosis were 68% and 72% respectively. The diagnostic accuracy was 70. Conclusion: the expression of mRNA and protein in PBMCs of AD patients was higher than that of healthy controls, although TREM2 could not be used as an independent marker of AD. But combined with other indicators can improve the diagnostic value of TREM2.
【学位授予单位】：青岛大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R749.16

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