Effects of soluble TREM2 on motor progression in Parkinson's disease

Abstract

Objectives: To determine whether sTREM2 is changed during the pathogenesis of PD and reflect motor decline in PD individuals.

Methods: The cerebrospinal fluid (CSF) from PD and healthy individuals were obtained to measure the expression of sTREM2 and further to evaluate the motor function at baseline and after four years of follow-up using the Parkinson's Progression Markers Initiative (PPMI) database. The relationship between motor disease progression at baseline and longitudinal CSF sTREM2 was evaluated by linear mixed-effects (LME) and multiple linear regression (MLR) models. The change rates of the motor symptoms and sTREM2 level in CSF were further rigorously analyzed using the LME model. Cox proportional-hazards regression models were used to evaluate the predictive values of sTREM2 in CSF for motor progression. The regulatory role of CSF α-syn and Tau between sTREM2 and motor assessments was evaluated by Mediating effect analysis.

Results: We found no significant difference in CSF sTREM2 levels between the PD and HC groups (p = 0.155). However, late-onset PD patients had higher CSF sTREM2 levels than early-onset PD patients (p = 0.044). The basal levels of sTREM2 could predict motor progression over the four years of follow-up. The change rate of CSF sTREM2 was correlated with the progressive deterioration of motor function in PD individuals. Our observations also showed that CSF Tau was a significant mediator of the association between CSF sTREM2 and total UPDRS scores and UPDRS III and tremor at baseline with 26.5% and 33.5%, and 28.7% mediation, respectively.

Conclusion: Our results indicated that CSF sTREM2 was associated with the prognosis of PD motor symptoms. Besides, CSF Tau could effectively mediate the association of sTREM2 with motor progression.

Keywords: Mediating effect analysis; Motor impairment; Parkinson’s disease; Regression analysis; Tau; sTREM2.