Investigation on Abnormal Iron Metabolism and Related Inflammation in Parkinson Disease Patients with Probable RBD

Yang Hu,Xiao-Min Wang,Li-Jun Zuo,Wei Zhang,Shu-Yang Yu,Ze-Jie Chen,Gai-Fen Liu,Ying-Shan Piao,Ya-Jie Wang,Piu Chan,Yang Du,Sheng-Di Chen,Chen-Jie Cao,Teng-Hong Lian,Fang Wang,Raffaele Ferri

doi:10.1371/journal.pone.0138997

Abstract

ObjectiveTo investigate potential mechanisms involving abnormal iron metabolism and related inflammation in Parkinson disease (PD) patients with probable rapid eye movement sleep behavior disorder (PRBD).MethodsTotal 210 PD patients and 31 controls were consecutively recruited. PD patients were evaluated by RBD Screening Questionnaire (RBDSQ) and classified into PRBD and probable no RBD (NPRBD) groups. Demographics information were recorded and clinical symptoms were evaluated by series of rating scales. Levels of iron and related proteins and inflammatory factors in cerebrospinal fluid (CSF) and serum were detected. Comparisons among control, NPRBD and PRBD groups and correlation analyses between RBDSQ score and levels of above factors were performed.Results(1)The frequency of PRBD in PD patients is 31.90%. (2)PRBD group has longer disease duration, more advanced disease stage, severer motor symptoms and more non-motor symptoms than NPRBD group. (3)In CSF, levels of iron, transferrin, NO and IL–1β in PRBD group are prominently increased. RBDSQ score is positively correlated with the levels of iron, transferrin, NO and IL–1β in PD group. Iron level is positively correlated with the levels of NO and IL–1β in PD group. (4)In serum, transferrin level is prominently decreased in PRBD group. PGE2 level in PRBD group is drastically enhanced. RBDSQ score exhibits a positive correlation with PGE2 level in PD group.ConclusionsPRBD is common in PD patients. PRBD group has severer motor symptoms and more non-motor symptoms. Excessive iron in brain resulted from abnormal iron metabolism in central and peripheral systems is correlated with PRBD through neuroinflammation.

Highlights

Parkinson disease (PD) is one of the most widespread neurodegenerative disorders with typical motor symptoms and a variety of non-motor symptoms
Excessive iron in brain resulted from abnormal iron metabolism in central and peripheral systems is correlated with probable rapid eye movement sleep behavior disorder (PRBD) through neuroinflammation
The level of transferrin, an iron metabolism-related protein, in brains of PD subjects is remarkably increased comparing with normal control subjects [7], indicating that abnormal iron metabolism in brain participate in the pathogenesis of PD

Summary

Introduction

Parkinson disease (PD) is one of the most widespread neurodegenerative disorders with typical motor symptoms and a variety of non-motor symptoms. The level of transferrin, an iron metabolism-related protein, in brains of PD subjects is remarkably increased comparing with normal control subjects [7], indicating that abnormal iron metabolism in brain participate in the pathogenesis of PD. The levels of iron and related proteins, such as ferritin, in cerebrospinal fluid (CSF) or serum were not different comparing with healthy control subjects reported by previous investigations [8,9]. No study detects the levels of iron and related proteins in CSF and serum in PD patients with RBD, and no investigation focuses on the correlation between RBD and iron metabolism in CSF and serum in PD patients

Methods

Results

Conclusion