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

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.

Serum sTREM2: A Potential Biomarker for Mild Cognitive Impairment in Patients With Obstructive Sleep Apnea

“…This indicates that serum sTREM2 has the potential to be a biomarker for MCI in OSA patients. These results were similar to previous studies ( Suárez-Calvet et al, 2016a , b ; Bekris et al, 2018 ; Ohara et al, 2019 ; Tanaka et al, 2019 ; Weber et al, 2020 ; Mo et al, 2021 ), although most tested sTREM2 levels in the CSF. In dementia and MCI, microglia in the central nervous system are activated and expression of TREM2 increases, with release of sTREM2 into the CSF.…”

“…It is a hot topic that sTREM2 may be a potential biomarker or therapeutic target for cognitive impairment caused by various diseases ( Suárez-Calvet et al, 2016a , b ; Ohara et al, 2019 ; Tanaka et al, 2019 ; Weber et al, 2020 ; Mo et al, 2021 ). However, little is known about the relationship between sTREM2 and OSA or OSA-related cognitive impairment.…”

“…However, the underlying mechanisms remain unclear. Previous studies have found that increased levels of CSF or plasma sTREM2 in neuroinflammatory diseases are related to the level of CSF or peripheral inflammatory factors ( Bekris et al, 2018 ; Rauchmann et al, 2020 ; Mo et al, 2021 ). The levels of inflammatory factors in OSA patients are increased because of the oxidative stress caused by intermittent hypoxia and sleep fragmentation ( Atrooz and Salim, 2019 ; Liu et al, 2020 ).…”

“…TREM2 releases its extracellular segment as a soluble form (sTREM2) into the extracellular space, which can be detected in the cerebrospinal fluid (CSF) and peripheral serum ( Wunderlich et al, 2013 ). It has been considered that the level of CSF sTREM2 is increased in patients with Alzheimer’s, and Parkinson’s diseases, even before symptom onset ( Suárez-Calvet et al, 2016a ; Mo et al, 2021 ; Morenas-Rodríguez et al, 2022 ). Recently, studies have found a significant association between increased serum/plasma sTREM2 levels and cognitive impairment in the elderly population, non-obese patients with diabetes, and young adults with Down syndrome ( Ohara et al, 2019 ; Tanaka et al, 2019 ; Weber et al, 2020 ).…”

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

“…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 ).…”