Yong Ren1, Houbo Jiang1, Jiali Pu1,2, Li Li1, Jianbo Wu1, Yaping Yan2, Guohua Zhao2, Thomas J Guttuso3, Baorong Zhang2, Jian Feng1. 1. Department of Physiology and Biophysics, State University of New York at Buffalo, Buffalo, New York, USA. 2. Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. 3. Department of Neurology, State University of New York at Buffalo, Buffalo, New York, USA.
Abstract
BACKGROUND: Despite intense efforts to develop an objective diagnostic test for Parkinson's disease, there is still no consensus on biomarkers that can accurately diagnose the disease. OBJECTIVE: Identification of biomarkers for idiopathic Parkinson's disease (PD) may enable accurate diagnosis of the disease. We tried to find molecular and cellular differences in dopaminergic (DA) neurons derived from healthy subjects and idiopathic PD patients with or without rest tremor at onset. METHODS: We measured the expression of genes controlling dopamine synthesis, sequestration, and catabolism as well as the levels of corresponding metabolites and reactive oxygen species in midbrain DA neurons differentiated from induced pluripotent stem cells (iPSCs) of healthy subjects and PD patients with or without rest tremor. RESULTS: Significant differences in DA-related gene expression, metabolites, and oxidative stress were found between midbrain DA neurons derived from healthy subjects and patients with PD. DA neurons derived from PD patients with or without rest tremor at onset exhibited significant differences in the levels of some of these transcripts, metabolites, and oxidative stress. CONCLUSION: The unique combination of these quantifiable molecular and cellular traits in iPSC-derived midbrain DA neurons can distinguish healthy subjects from idiopathic PD patients and segregate PD patients with or without rest tremor at onset. The strategy may be used to develop an objective diagnostic test for PD.
BACKGROUND: Despite intense efforts to develop an objective diagnostic test for Parkinson's disease, there is still no consensus on biomarkers that can accurately diagnose the disease. OBJECTIVE: Identification of biomarkers for idiopathic Parkinson's disease (PD) may enable accurate diagnosis of the disease. We tried to find molecular and cellular differences in dopaminergic (DA) neurons derived from healthy subjects and idiopathic PD patients with or without rest tremor at onset. METHODS: We measured the expression of genes controlling dopamine synthesis, sequestration, and catabolism as well as the levels of corresponding metabolites and reactive oxygen species in midbrain DA neurons differentiated from induced pluripotent stem cells (iPSCs) of healthy subjects and PD patients with or without rest tremor. RESULTS: Significant differences in DA-related gene expression, metabolites, and oxidative stress were found between midbrain DA neurons derived from healthy subjects and patients with PD. DA neurons derived from PD patients with or without rest tremor at onset exhibited significant differences in the levels of some of these transcripts, metabolites, and oxidative stress. CONCLUSION: The unique combination of these quantifiable molecular and cellular traits in iPSC-derived midbrain DA neurons can distinguish healthy subjects from idiopathic PD patients and segregate PD patients with or without rest tremor at onset. The strategy may be used to develop an objective diagnostic test for PD.
Authors: Ronald B Postuma; Daniela Berg; Matthew Stern; Werner Poewe; C Warren Olanow; Wolfgang Oertel; José Obeso; Kenneth Marek; Irene Litvan; Anthony E Lang; Glenda Halliday; Christopher G Goetz; Thomas Gasser; Bruno Dubois; Piu Chan; Bastiaan R Bloem; Charles H Adler; Günther Deuschl Journal: Mov Disord Date: 2015-10 Impact factor: 10.338