Substantia Nigra Dysregulated Gene Spectra and Blood Biomarkers for Parkinson's Disease

Background: Parkinson's disease (PD) is a common and complex neurodegenerative disease with an elusive etiologies. Both molecular mechanisms and biomarkers remain to be further uncovered in PD. Methods: Qualified human microarray datasets of the substantia nigra and blood were acquired from PD case-control studies. A discovery and replication two-phase method was used to identify dysregulated genes with functional enrichment analyses. An integrated analysis was used to screen PD biomarkers followed by validations in blood samples of 50 PD patients and 50 controls. Findings: Eight datasets of substantia nigra and 3 datasets of blood were retrieved, including 21 million data points from 146 substantia nigra and 571 blood samples. A total of 5 up-regulated genes and 91 down-regulated genes (fold-change > 1.5 and P 1.2 and P < 0.05. TUBB2A in reduced expression decently predicted PD as a blood biomarker (sensitivity, 0.72; specificity, 0.70; AUC, 0.730 [95% CI, 0.632-0.828]). Interpretation: Our study provides novel insight into elucidating mechanisms underlying PD pathophysiology and the development of promising PD biomarkers. Funding: This work was supported by funding from Zhejiang Provincial Natural Science Foundation (LD19H090001 and LZ19H090002), National Natural Science Foundation of China (81571087, 81771380, and 81771510), and Wenzhou Municipal Science and Technology Bureau (C20170003). Declaration of Interest: The authors declare that there is no actual or potential conflict of interest. Ethical Approval: All participants provided written informed consent. The study was approved by the ethics committee of the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University.