title: microRNA Profiles in Parkinson's Disease Prefrontal Cortex.
abstract: OBJECTIVE
  The goal of this study was to compare the microRNA (miRNA) profile of Parkinson's disease (PD) frontal cortex with normal control brain, allowing for the identification of PD specific signatures as well as study the disease-related phenotypes of onset age and dementia.
  
  
  METHODS
  Small RNA sequence analysis was performed from prefrontal cortex for 29 PD samples and 33 control samples. After sample QC, normalization and batch correction, linear regression was employed to identify miRNAs altered in PD, and a PD classifier was developed using weighted voting class prediction. The relationship of miRNA levels to onset age and PD with dementia (PDD) was also characterized in case-only analyses.
  
  
  RESULTS
  One twenty five miRNAs were differentially expressed in PD at a genome-wide level of significance (FDR q < 0.05). A set of 29 miRNAs classified PD from non-diseased brain (93.9% specificity, 96.6% sensitivity). The majority of differentially expressed miRNAs (105/125) showed an ordinal relationship from control, to PD without dementia (PDN), to PDD. Among PD brains, 36 miRNAs classified PDD from PDN (sensitivity = 81.2%, specificity = 88.9%). Among differentially expressed miRNAs, miR-10b-5p had a positive association with onset age (q = 4.7e-2).
  
  
  CONCLUSIONS
  Based on cortical miRNA levels, PD brains were accurately classified from non-diseased brains. Additionally, the PDD miRNA profile exhibited a more severe pattern of alteration among those differentially expressed in PD. To evaluate the clinical utility of miRNAs as potential clinical biomarkers, further characterization and testing of brain-related miRNA alterations in peripheral biofluids is warranted.
authors.affiliation: Department of Neurology, Boston University School of MedicineBoston, MA, USA; Graduate Program in Genetics and Genomics, Boston University School of MedicineBoston, MA, USA.
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Hoss
authors.affiliation: Department of Neurology, Boston University School of MedicineBoston, MA, USA; Bioinformatics Program, Boston UniversityBoston, MA, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Labadorf
authors.affiliation: Banner Sun Health Research Institute Sun City, AZ, USA.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Beach
authors.affiliation: Department of Neurology, Boston University School of Medicine Boston, MA, USA.
authors.forename: Jeanne C
authors.initials: JC
authors.lastname: Latourelle
authors.affiliation: Department of Neurology, Boston University School of MedicineBoston, MA, USA; Graduate Program in Genetics and Genomics, Boston University School of MedicineBoston, MA, USA; Bioinformatics Program, Boston UniversityBoston, MA, USA; Genome Science Institute, Boston University School of MedicineBoston, MA, USA.
authors.forename: Richard H
authors.initials: RH
authors.lastname: Myers
keywords: Huntington's disease; Parkinson's disease; cortex; dementia; miRNA; small RNA sequencing