title: MicroRNA Profile in Patients with Alzheimer's Disease: Analysis of miR-9-5p and miR-598 in Raw and Exosome Enriched Cerebrospinal Fluid Samples.
abstract: MicroRNAs have been postulated as potential biomarkers for Alzheimer's disease (AD). Exosomes are nanovesicles which transport microRNAs, proteins, and other cargos. It has been hypothesized that the exosome traffic might be increased in neurodegenerative disorders.
  
  
  
  i) To assess the cerebrospinal fluid (CSF) microRNA profile in a group of AD patients and control subjects and to validate a group of microRNAs previously reported by other authors. ii) To compare microRNA levels in whole CSF and in the exosome-enriched fraction in AD patients.
  
  
  
  A panel of 760 microRNAs was analyzed in the CSF of 10 AD patients and 10 healthy subjects. Among microRNAs differently expressed, we selected those that had been previously reported by other authors. Candidates were validated in a larger group by individual qPCR assays. MicroRNA expression was also evaluated in exosome-enriched CSF samples of patients with AD and controls.
  
  
  
  Fifteen microRNAs were differently expressed in AD. MiR-9-5p, miR-134, and miR-598 were selected as candidates for further analysis. MiR-9-5p and miR-598 were detected in 50 and 75% of control CSF samples, respectively, while they were not detected in any AD CSF samples. We observed an opposite pattern when we evaluated the microRNA expression in the exosome-enriched CSF AD samples. No pattern variations were noted among healthy subjects.
  
  
  
  These data propose miR-9-5p and miR-598 as potential biomarkers for AD. Further studies in plasma and other body fluids will confirm their potential role as easily accessible biomarkers. In addition, our data suggest that exosome trafficking is different between AD and control subjects raising the need to take this phenomenon into consideration in future studies of AD biomarkers.
authors.affiliation: Service of Neurology, University Hospital Marqués de Valdecilla -IDIVAL; CIBERNED, Santander, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Riancho
authors.affiliation: Service of Neurology, University Hospital Marqués de Valdecilla -IDIVAL; CIBERNED, Santander, Spain.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Vázquez-Higuera
authors.affiliation: Service of Neurology, University Hospital Marqués de Valdecilla -IDIVAL; CIBERNED, Santander, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Pozueta
authors.affiliation: Service of Neurology, University Hospital Marqués de Valdecilla -IDIVAL; CIBERNED, Santander, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Lage
authors.affiliation: Service of Neurology, University Hospital Marqués de Valdecilla -IDIVAL; CIBERNED, Santander, Spain.
authors.forename: Martha
authors.initials: M
authors.lastname: Kazimierczak
authors.affiliation: Service of Neurology, University Hospital Marqués de Valdecilla -IDIVAL; CIBERNED, Santander, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Bravo
authors.affiliation: CIBERNED; National Institute of Health Carlos III; Alzheimer Disease Research Unit, CIEN Foundation; Queen Sofia Foundation Alzheimer Center; Chronic Disease Programme Carlos III Institute of Health, Madrid, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Calero
authors.affiliation: Service of Neurology, University Hospital Marqués de Valdecilla -IDIVAL; CIBERNED, Santander, Spain.
authors.forename: Andrea
authors.initials: A
authors.lastname: Gonalezález
authors.affiliation: Service of Neurology, University Hospital Marqués de Valdecilla -IDIVAL; CIBERNED, Santander, Spain.
authors.forename: Eloy
authors.initials: E
authors.lastname: Rodríguez
authors.affiliation: Department of Neurology, Memory Unit, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; CIBERNED.
authors.forename: Alberto
authors.initials: A
authors.lastname: Lleó
authors.affiliation: Service of Neurology, University Hospital Marqués de Valdecilla -IDIVAL; CIBERNED, Santander, Spain.
authors.forename: Pascual
authors.initials: P
authors.lastname: Sánchez-Juan
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D015331:Cohort Studies; D055354:Exosomes / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000134:cerebrospinal fluid*; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D015415:Biomarkers; C054369:MAPT protein, human; C000619454:MIRN-598 microRNA, human; C569273:MIRN134 microRNA, human; C541874:MIRN92 microRNA, human; D035683:MicroRNAs; D016875:tau Proteins
keywords: Alzheimer’s disease; biomarkers; exosomes; microRNAs