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

Peng, Gongyong; Qiu, Jingjun; Liu, Hanqun; Zhou, Miaomiao; Huang, Shuxuan; Guo, Wenyuan; Lin, Yuwan; Chen, Xiang; Li, Zhe; Li, Guihua; Zhang, Wenlong; Zhang, Yunlong; Li, Xingjian; Wu, Zhuohua; Wei, Lei; Yang, Xinling; Zhu, Xiaodong; Mo, Mingshu; Xu, Pingyi

doi:10.1007/s12031-019-01424-7

Cited by 18 publications

(14 citation statements)

References 39 publications

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“…It suggests that TREM2 may contribute to microglial recognition and endocytosis of α-syn. In our study, we found that the levels of sTREM2 in the CSF of PD patients were higher than those of controls and positively correlated with the levels of α-syn in the CSF, an association previously observed in PD patients ( Peng et al, 2020 ). We found that an elevated concentration of sTREM2 in CSF may help to differentiate PD patients from healthy controls with an AUC of 0.791 (CI = 0.711–0.871).…”

Section: Discussionsupporting

confidence: 85%

“…The concentrations of sTREM2 and α-syn were detected by enzyme-linked immunosorbent assay (ELISA) as previously described ( Peng et al, 2020 ). After the freeze-thaw cycles, the Human TREM2 DuoSet ELISA (R&D Systems: #DY1828–05, Minneapolis, MN, United States) and Human alpha-Synuclein DuoSet ELISA (R&D Systems: #DY1338–05, Minneapolis, MN, United States) were used to measure the concentration of sTREM2 and α-syn in the CSF according to the manufacturer’s instructions ( Peng et al, 2020 ). Briefly, 96-well streptavidin plates were blocked with 3% bovine serum albumin (BSA) and coated with the capture antibodies.…”

Section: Methodsmentioning

confidence: 99%

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Soluble Triggering Receptor Expressed on Myeloid Cells 2 From Cerebrospinal Fluid in Sleep Disorders Related to Parkinson’s Disease

Tang

Wei

et al. 2021

Front. Aging Neurosci.

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Background: Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglial receptor exclusively expressed in the central nervous system (CNS). It contributes to abnormal protein aggregation in neurodegenerative disorders, but its role in Parkinson’s disease (PD) is still unclear.Methods: In this case-control study, we measured the concentration of the soluble fragment of TREM2 (sTREM2) in PD patients, evaluated their sleep conditions by the PD sleep scale (PDSS), and analyzed the relationship between sTREM2 and PD symptoms.Results: We recruited 80 sporadic PD patients and 65 healthy controls without disease-related variants in TREM2. The concentration of sTREM2 in the CSF was significantly higher in PD patients than in healthy controls (p < 0.01). In the PD group, the concentration of sTREM2 had a positive correlation with α-syn in the CSF (Pearson r = 0.248, p = 0.027). Receiver operating characteristic curve (ROC) analyses showed that sTREM2 in the CSF had a significant diagnostic value for PD (AUC, 0.791; 95% CI, 0.711–0.871, p < 0.05). The subgroup analysis showed that PD patients with sleep disorders had a significantly higher concentration of sTREM2 in their CSF (p < 0.01). The concentration of sTREM2 in the CSF had a negative correlation with the PDSS score in PD patients (Pearson r = −0.555, p < 0.01). The ROC analyses showed that sTREM2 in the CSF had a significant diagnostic value for sleep disorders in PD (AUC, 0.733; 95% CI, 0.619–0.846, p < 0.05).Conclusion: Our findings suggest that CSF sTREM2 may be a potential biomarker for PD and it could help predict sleep disorders in PD patients, but multicenter prospective studies with more participants are still needed to confirm its diagnostic value in future.

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Section: Discussionsupporting

confidence: 85%

Section: Methodsmentioning

confidence: 99%

Soluble Triggering Receptor Expressed on Myeloid Cells 2 From Cerebrospinal Fluid in Sleep Disorders Related to Parkinson’s Disease

Tang

Wei

et al. 2021

Front. Aging Neurosci.

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“…Due to the neuroinflammation in the SN induced by MPTP and rotenone, it may be necessary to detect the expression of soluble triggering receptor expressed on myeloid cells 2 (TREM2) in future studies, since soluble TREM2 in the cerebrospinal fluid (CSF) has been revealed to be a biomarker of neurodegeneration and glial activation in Alzheimer's disease ( 70 ). In several recent studies, soluble TREM2 in CSF has been reported as a potential biomarker of neuronal injury in Parkinson's disease ( 71 – 73 ).…”

Section: Discussionmentioning

confidence: 99%

Comparison of the effect of rotenone and 1‑methyl‑4‑phenyl‑1,2,3,6‑tetrahydropyridine on inducing chronic Parkinson's disease in mouse models

et al. 2022

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“…Infection of the midbrain with an adeno-associated virus vector overexpressing a -Syn and inoculation of preformed a -Syn fibrils into the striatum effectively induced DA neurodegeneration (72,73). Compared with healthy controls, sTREM2 in CSF of PD patients was upregulated and positively correlated with total a-Syn degradation (74). Whether sTREM2 was related to a-Syn degradation remains to be studied.…”

Section: Trem2 and A-synmentioning

confidence: 99%

“…Since sTREM2 expression in CSF was increased in PD patients and was positively correlated with total a-Syn in CSF (74), it was suggested that sTREM2 in CSF could be used as a substitute immune biomarker for PD neuron injury. Studies have shown that the misdiagnosis rate of PD was about 25% (125), and correct biomarkers were conducive to the prevention and diagnosis of PD.…”

Section: Trem2 Treatmentmentioning

confidence: 99%

Targeting TREM2 for Parkinson’s Disease: Where to Go?

Zhang

2021

Front. Immunol.

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Parkinson’s disease (PD) is one of most common neurodegenerative disorders caused by a combination of environmental and genetic risk factors. Currently, numerous population genetic studies have shown that polymorphisms in myeloid cell-triggered receptor II (TREM2) are associated with a variety of neurodegenerative disorders. Recently, TREM2 has been verified to represent a promising candidate gene for PD susceptibility and progression. For example, the expression of TREM2 was apparently increased in the prefrontal cortex of PD patients. Moreover, the rare missense mutations in TREM2 (rs75932628, p.R47H) was confirmed to be a risk factor of PD. In addition, overexpression of TREM2 reduced dopaminergic neurodegeneration in the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine mouse model of PD. Due to the complex pathogenesis of PD, there is still no effective drug treatment. Thus, TREM2 has received increasing widespread attention as a potential therapeutic target. This review focused on the variation of TREM2 in PD and roles of TREM2 in PD pathogenesis, such as excessive-immune inflammatory response, α-Synuclein aggregation and oxidative stress, to further provide evidence for new immune-related biomarkers and therapies for PD.

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

Cited by 18 publications

References 39 publications

Soluble Triggering Receptor Expressed on Myeloid Cells 2 From Cerebrospinal Fluid in Sleep Disorders Related to Parkinson’s Disease

Soluble Triggering Receptor Expressed on Myeloid Cells 2 From Cerebrospinal Fluid in Sleep Disorders Related to Parkinson’s Disease

Comparison of the effect of rotenone and 1‑methyl‑4‑phenyl‑1,2,3,6‑tetrahydropyridine on inducing chronic Parkinson's disease in mouse models

Targeting TREM2 for Parkinson’s Disease: Where to Go?

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