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Analysis of Cerebrospinal Fluid Soluble TREM2 and Polymorphisms in Sporadic Parkinson’s Disease in a Chinese Population

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Abstract

Background

Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglial surface receptor that mediates the degradation disorder of amyloid β (Aβ) in Alzheimer’s disease. However, the role of TREM2 in Parkinson’s disease (PD) and α-Synclein (α-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-α-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.

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Acknowledgments

This work was supported by research grants from the National Key R&D Program of China (2016YFC1306601, 2017YFC1306002), National Natural Science Foundation of China (81701254, 81430021, 81771401, 81870992, U1503222, U1603281), a technology project of Guangzhou (201504281820463, 2018-1202-SF-0019), China Postdoctoral Science Foundation (2018 M633031), and a grant from Nature Science Foundation of Guangdong Province (2018A030313649, A2018315).

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Authors and Affiliations

  1. Department of Neurology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 511436, China

    Guoyou Peng, Jiewen Qiu, Hanqun Liu, Miaomiao Zhou, Shuxuan Huang, Wenyuan Guo, Yuwan Lin, Xiang Chen, Zhe Li, Guihua Li, Wenlong Zhang, Xingjian Li, Zhuohua Wu, Mingshu Mo & Pingyi Xu

  2. Department of Physiology, Guangzhou Medical University, Guangzhou, 511436, China

    Yunlong Zhang & Xiaoqin Zhu

  3. Neuroscience Center, Guangzhou Medical University, Guangzhou, 511436, China

    Yunlong Zhang, Xiaoqin Zhu & Pingyi Xu

  4. Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China

    Lei Wei

  5. Department of Neurology, The Second Affiliated Hospital of Xinjiang Medical University, Urumqi, 830011, China

    Xinling Yang

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  1. Guoyou Peng
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  2. Jiewen Qiu
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  4. Miaomiao Zhou
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Correspondence to Xiaoqin Zhu, Mingshu Mo or Pingyi Xu.

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Guoyou Peng, Jiewen Qiu, and Hanqun Liu contributed equally to this work.

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Fig. S1

Relationship between sTREM2 and gender and age in PD patients. CSF-sTREM2 levels did not differ between male and female PD patients (A) and healthy controls (B) based on the Mann–Whitney test. CSF-sTREM2 levels were positively correlated with age in PD patients (C) but not in healthy controls (D) based on the results of Pearson-correlation analysis. E and F sTREM2 levels in the CSF did not show any correlation with those in plasma based on the results of Pearson-correlation analysis. Pearson-correlation coefficients were used for correlational analyses (PNG 216 kb)

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Peng, G., Qiu, J., Liu, H. et al. Analysis of Cerebrospinal Fluid Soluble TREM2 and Polymorphisms in Sporadic Parkinson’s Disease in a Chinese Population. J Mol Neurosci 70, 294–301 (2020). https://doi.org/10.1007/s12031-019-01424-7

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