Superfund Research Program
Plasma Biomarkers for Parkinsonism in Welders
Project Leader: Jing Zhang
Grant Number: P42ES004696
Funding Period: 2009-2015
- Project Summary
Final Progress Reports
The major aim of this project seeks to identify novel peripheral biomarkers of parkinsonism (PS) in occupational welders exposed to fumes containing manganese (Mn), a metal long known to be neurotoxic. This study is closely related to the Parkinsonism and Metal Exposures Among Welders project (Dr. Checkoway) in that blood and plasma specimens utilized for this work are collected from participants of the epidemiologic study.
In the current funding cycle, Dr. Zhang and his research team identified autoantibodies against mortalin, a protein previously identified by his lab to be decreased in Parkinson disease (PD), as being increased in the plasma of PD patients when compared to controls. Furthermore, they found a positive correlation of mortalin autoantibody level with PD severity as assessed by the Unified Parkinson Disease Rating Scale motor subscore 3 (UPDRS3). When applying this candidate biomarker to welders with and without PS, they observed a tendency for the mortalin autoantibody to increase in subjects with higher UPDRS3 scores, although the correlation was much weaker than that of the PD patients. This may be explained by the fact that the studied PD patients generally score much higher on the UPDRS3 scale than the studied welders. In this regard, future longitudinal studies will be very informative in determining whether or not autoantibodies against mortalin represent a peripheral biomarker of PS severity and in ascertaining their potential to play a role in disease etiology.
The research group recently contributed a significant technological advance to the field of peripheral biomarkers for neurodegenerative disease by isolating plasma exosomes that most likely originate in the central nervous system (CNS). This technique allows them to study the behavior of proteins within the brain via a minimally invasive blood draw. Their initial findings utilizing this technology identified increased α-synuclein, a protein centrally involved in PD pathogenesis, in CNS exosomes of PD patients. Finally, they have isolated mRNAs and ncRNAs in the CNS-derived exosomes. This finding highlights the potential of the technology and its implications for identifying biomarkers of early PS under minimally invasive conditions.