title: Decreased Expression of hsa-miR-4274 in Cerebrospinal Fluid of Normal Pressure Hydrocephalus Mimics with Parkinsonian Syndromes.
abstract: Patients presenting with the classical idiopathic normal pressure hydrocephalus (iNPH) triad often show additional parkinsonian spectrum signs. Accurate differential diagnosis strongly influences the long-term outcome of cerebrospinal fluid (CSF) shunting.
  
  
  
  The aim of this study was to find potential CSF microRNA (miRNA) biomarkers for NPH mimics with parkinsonian syndromes that can reliably distinguish them from iNPH patients.
  
  
  
  Two cohorts of 81 patients (cohort 1, n = 55; cohort 2, n = 26) with possible iNPH who were treated in two centers between January 2011 and May 2014 were studied. In both cohorts, CSF samples were obtained from patients clinically diagnosed with iNPH (n = 21 and n = 10, respectively), possible iNPH with parkinsonian spectrum (PS) (n = 18, n = 10, respectively), possible iNPH with Alzheimer's disease (AD) (n = 16), and non-affected elderly individuals (NC) (n = 6). A three-step qRT-PCR analysis of the CSF samples was performed to detect miRNAs that were differentially expressed in the groups.
  
  
  
  The expression of hsa-miR-4274 in CSF was decreased in both cohorts of PS group patients (cohort 1: p < 0.0001, cohort 2: p < 0.0001), and was able to distinguish PS from iNPH with high accuracy (area under the curve = 0.908). The CSF concentration of hsa-miR-4274 also correlated with the specific binding ratio of ioflupane (123I) dopamine transporter scan (r = -0.494, p = 0.044). By contrast, the level of hsa-miR-4274 was significantly increased in the PS group after CSF diversion.
  
  
  
  Levels of CSF hsa-miR-4274 can differentiate PS from patients with iNPH, AD, and NC. This may be clinically useful for diagnostic purposes and predicting shunt treatment responses.
authors.affiliation: Department of Neurosurgery, Juntendo University Graduate School of Medicine, Tokyo, Japan.|Department of Pharmacology and Department of Neurology, University of Zagreb School of Medicine, Zagreb, Croatia.
authors.forename: Ivana
authors.initials: I
authors.lastname: Jurjević
authors.affiliation: Department of Neurosurgery, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Miyajima
authors.affiliation: Department of Neurosurgery, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Ikuko
authors.initials: I
authors.lastname: Ogino
authors.affiliation: Department of Neurosurgery, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Akiba
authors.affiliation: Department of Neurosurgery, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Madoka
authors.initials: M
authors.lastname: Nakajima
authors.affiliation: Department of Neurosurgery, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Akihide
authors.initials: A
authors.lastname: Kondo
authors.affiliation: Division of Proteomics and Bio Molecular Science, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Kikkawa
authors.affiliation: Department of Neurology, Takasaki General Medical Center, Gunma, Japan.
authors.forename: Mitsuyasu
authors.initials: M
authors.lastname: Kanai
authors.affiliation: Department of Neurology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Hattori
authors.affiliation: Department of Neurosurgery, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Arai
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D016564:Amyloid beta-Protein Precursor / Q000134:cerebrospinal fluid; D015331:Cohort Studies; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D006850:Hydrocephalus, Normal Pressure / Q000134:cerebrospinal fluid* / Q000150:complications*; D008297:Male; D035683:MicroRNAs / Q000134:cerebrospinal fluid* / Q000235:genetics*; D020734:Parkinsonian Disorders / Q000503:physiopathology*; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D012333:RNA, Messenger / Q000378:metabolism; D051844:alpha-Synuclein / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D035683:MicroRNAs; D010446:Peptide Fragments; D012333:RNA, Messenger; D051844:alpha-Synuclein; C075222:amyloid beta-protein (1-42)
keywords: Alzheimer’s disease; cerebrospinal fluid; idiopathic normal pressure hydrocephalus; microRNAs; parkinsonian syndrome