title: Transcriptomic Profiling of Extracellular RNAs Present in Cerebrospinal Fluid Identifies Differentially Expressed Transcripts in Parkinson's Disease.
abstract: BACKGROUND
  Parkinson's disease (PD) is a debilitating neurological disorder for which prognostic and diagnostic biomarkers are lacking. Cerebrospinal fluid (CSF) is an accessible body fluid that comes into direct contact with the central nervous system (CNS) and acts as a nuclease-free repository where RNA transcripts shed by brain tissues can reside for extended periods of time.
  
  
  OBJECTIVE
  We studied the RNA species present in the CSF of PD patients to identify novel diagnostic biomarkers.
  
  
  METHODS
  Small volumes of CSF from 27 PD patients and 30 healthy age- and sex-matched controls were used for RNA extraction followed by next-generation sequencing (RNA-seq) using the Illumina platform. CSF contains a number of fragmented RNA species that were individually sequenced and analyzed. Comparing PD to control subjects, we observed a pool of dysregulated sequencing tags that were further analyzed and validated by quantitative real-time PCR (qRT-PCR).
  
  
  RESULTS
  A total of 201 differentially expressed sequencing tags (DETs), including 92 up-regulated and 109 down-regulated DETs were identified. We validated the following DETs by real time PCR in the patient samples: Dnmt1, Ezh2, CCR3, SSTR5,PTPRC, UBC, NDUFV2, BMP7, SCN9, SCN9 antisense (AC010127.3), and long noncoding RNAs AC079630 and UC001lva.4 (close to the LRRK2 gene locus), as potential PD biomarkers.
  
  
  CONCLUSIONS
  The CSF is a unique environment that contains many species of RNA. Our work demonstrates that CSF can potentially be used to identify biomarkers for the detection and tracking of disease progression and evaluation of therapeutic outcomes.
authors.affiliation: Department of Psychiatry & Behavioral Sciences, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Arash
authors.initials: A
authors.lastname: Hossein-Nezhad
authors.affiliation: Department of Psychiatry & Behavioral Sciences, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Roya Pedram
authors.initials: RP
authors.lastname: Fatemi
authors.affiliation: Department of Psychiatry & Behavioral Sciences, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Rili
authors.initials: R
authors.lastname: Ahmad
authors.affiliation: Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA, USA.|Mental Illness Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA.
authors.forename: Elaine R
authors.initials: ER
authors.lastname: Peskind
authors.affiliation: Geriatric Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA.|Parkinson's Disease Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA.|Department of Neurology, University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: Cyrus P
authors.initials: CP
authors.lastname: Zabetian
authors.affiliation: Geriatric Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA.|Parkinson's Disease Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA.|Department of Neurology, University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: Shu-Ching
authors.initials: SC
authors.lastname: Hu
authors.affiliation: Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Shi
authors.affiliation: Department of Psychiatry & Behavioral Sciences, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Claes
authors.initials: C
authors.lastname: Wahlestedt
authors.affiliation: Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Psychiatry & Behavioral Sciences, University of Miami Miller School of Medicine, Miami, FL, USA.|John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Mohammad Ali
authors.initials: MA
authors.lastname: Faghihi
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000134:cerebrospinal fluid* / Q000235:genetics; D012313:RNA / Q000134:cerebrospinal fluid*; D060888:Real-Time Polymerase Chain Reaction; D059467:Transcriptome / Q000235:genetics
chemical_list: D015415:Biomarkers; D012313:RNA
keywords: Parkinson disease; RNA sequencing; biomarkers; cerebrospinal fluid; long noncoding RNA