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

Mingshu Mo,Xiaoqin Zhu,Zhuohua Wu,Wei Dai,Xiang Chen,Zhiling Zhang,Guoyou Peng,Yuwan Lin,Panghai Ye,Miaomiao Zhou,Yijuan Wu,Jiewen Qiu,Liuyan Ding,Yuting Tang,Lijian Wei,Hanqun Liu,Pingyi Xu,Wenyuan Guo

doi:10.3389/fnagi.2021.753210

Abstract

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.

Highlights

Parkinson’s disease (PD) is a common neurodegenerative disease that is characterized by an impaired dopaminergic (DA) neurotransmitter system, aggregation of α-synuclein (α-syn) and microglial neuroinflammation-mediated neuroinflammation in the midbrain (Block and Hong, 2005; Wang et al, 2015; Rai and Singh, 2020; Rai et al, 2021)
We found that higher sTREM2 levels were correlated with worse sleep disorders, as measured by the PD sleep scale (PDSS) scale
We found that an elevated concentration of sTREM2 in CSF may help to differentiate PD patients from healthy controls with an area under the ROC curve (AUC) of 0.791 (CI = 0.711– 0.871)

Summary

Introduction

Parkinson’s disease (PD) is a common neurodegenerative disease that is characterized by an impaired dopaminergic (DA) neurotransmitter system, aggregation of α-synuclein (α-syn) and microglial neuroinflammation-mediated neuroinflammation in the midbrain (Block and Hong, 2005; Wang et al, 2015; Rai and Singh, 2020; Rai et al, 2021). In addition to motor symptoms, PD patients suffer from non-motor disorders such as sleep disorders (Stefani and Högl, 2020). Sleep disorders affect 60– 98% of PD patients as one of the most common non-motor symptoms and it often appears as the first symptom (Chaudhuri et al, 2006; Stefani and Högl, 2020). 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

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Discussion

Conclusion