Analysis of Cerebrospinal Fluid Soluble TREM2 and Polymorphisms in Sporadic Parkinson's Disease in a Chinese Population
Analysis of Cerebrospinal Fluid Soluble TREM2 and Polymorphisms in Sporadic Parkinson's Disease in a Chinese Population
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中国人群散发性帕金森病脑脊液可溶性TREM2及多态性分析
DOI：
10.1007/s12031-019-01424-7
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发表时间：
2019-12-12
影响因子：
3.1
通讯作者：
Xu, Pingyi
中科院分区：
文献类型：
--
作者：
Peng, Guoyou;Qiu, Jiewen;Xu, Pingyi
髓样细胞触发受体2（Triggeringreceptorexpressedonmyeloidcells 2，TREM 2）是一种小胶质细胞表面受体，介导阿尔茨海默病中β淀粉样蛋白（amyloidbeta，A β）的降解紊乱。然而，TREM 2在帕金森病（PD）和α-Synclein（alpha-Syn）降解中的作用在很大程度上尚不清楚。方法采用桑格（Sanger）测序法，对1,292例PD患者（n = 612）和680例健康对照者（n = 680）的TREM 2基因第2外显子的多态性进行测序，采用Fisher精确检验比较两组间等位基因频率分布。此外，我们开发并使用酶联免疫吸附试验来评估脑脊液（CSF）中可溶性TREM 2（sTREM 2）的水平，并分析部分测序组（55名PD和40名健康对照）的血浆中sTREM 2与总α-Syn（t-a-Syn）的关系。结果在612例PD患者和680例健康对照者中，检测到TREM 2基因第2外显子的两个新变异，即p.S81N和p.G58D，但与PD无显著相关性。与健康对照相比，CSF中的sTREM 2在PD患者中显著上调（433.1 +/-24.7 pg/mL vs.275.2 +/-17.9 pg/mL，p < 0.0001），但在血浆中不显著上调（281.7 +/-29.3 pg/mL vs.257.8 +/-16.5 pg/mL，p = 0.805）。在PD患者中，sTREM 2与CSF中的t-alpha-syn（r = 0.62，p = 0.0001）呈正相关，但与血浆中的t-alpha-syn（r = 0.02，p = 0.89）无关。结论虽然不能说明TREM 2基因外显子2多态性在中国人PD发病中起作用，但我们的研究结果提示CSF sTREM 2作为一种有前景的生物标志物，极有可能成为PD治疗的新靶点。
Background Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglial surface receptor that mediates the degradation disorder of amyloid beta (A beta) in Alzheimer's disease. However, the role of TREM2 in Parkinson's disease (PD) and alpha-Synclein (alpha-Syn) degradation is largely unknown. Methods In this case-control study on Chinese population, we sequenced for polymorphisms in exon 2 of the TREM2 gene in 1,292 individuals, PD cases (n = 612), healthy controls (n = 680) by Sanger sequence, and compared the distribution of allelic frequencies between the two groups by the Fisher's exact test. Additionally, we developed and used the enzyme-linked immunosorbent assay to evaluated soluble TREM2 (sTREM2) levels in the cerebrospinal fluid (CSF), and plasma in partial of sequenced groups (55 PD and 40 healthy controls) analyzed their relationship with total a-syn (t-a-Syn). Results Two novel variants were detected in exon 2 of the TREM2 gene, namely, p.S81 N, p.G58D; however, these were not significantly associated with PD (612 PD and 680 healthy controls). sTREM2 in CSF was significantly upregulated in PD patients compared to healthy controls (433.1 +/- 24.7 pg/mL vs. 275.2 +/- 17.9 pg/mL, p < 0.0001), but not in plasma (281.7 +/- 29.3 pg/mL vs. 257.8 +/- 16.5 pg/mL, p = 0.805). In PD patients, sTREM2 was positively correlated with t-alpha-syn (r = 0.62, p = 0.0001) in CSF, but not in plasma (r = 0.02, p = 0.89). Conclusions Although it may not indicate that exon 2 polymorphisms of TREM2 play a role in the pathogenesis of PD in the Chinese population, our findings described above highlight the relevance of CSF sTREM2 as a promising biomarker and are extremely possible to the therapeutic target for PD in the future.