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dc.contributor.authorSchneider, Raphael
dc.contributor.authorMcKeever, Paul
dc.contributor.authorKim, TaeHyung
dc.contributor.authorGraff, Caroline
dc.contributor.authorvan Swieten, John Cornelis
dc.contributor.authorKarydas, Anna
dc.contributor.authorBoxer, Adam
dc.contributor.authorRosen, Howie
dc.contributor.authorMiller, Bruce L
dc.contributor.authorLaforce, Robert
dc.contributor.authorGalimberti, Daniela
dc.contributor.authorMasellis, Mario
dc.contributor.authorBorroni, Barbara
dc.contributor.authorZhang, Zhaolei
dc.contributor.authorZinman, Lorne
dc.contributor.authorRohrer, Jonathan Daniel
dc.contributor.authorTartaglia, Maria Carmela
dc.contributor.authorRobertson, Janice
dc.contributor.authorGenetic FTD Initiative (GENFI)
dc.date.accessioned2018-05-10T15:32:28Z
dc.date.available2018-05-10T15:32:28Z
dc.date.issued2018-08
dc.identifier.issn0022-3050
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/275703
dc.description.abstractOBJECTIVE: To determine whether exosomal microRNAs (miRNAs) in cerebrospinal fluid (CSF) of patients with frontotemporal dementia (FTD) can serve as diagnostic biomarkers, we assessed miRNA expression in the Genetic Frontotemporal Dementia Initiative (GENFI) cohort and in sporadic FTD. METHODS: GENFI participants were either carriers of a pathogenic mutation in progranulin, chromosome 9 open reading frame 72 or microtubule-associated protein tau or were at risk of carrying a mutation because a first-degree relative was a known symptomatic mutation carrier. Exosomes were isolated from CSF of 23 presymptomatic and 15 symptomatic mutation carriers and 11 healthy non-mutation carriers. Expression of 752 miRNAs was measured using quantitative PCR (qPCR) arrays and validated by qPCR using individual primers. MiRNAs found differentially expressed in symptomatic compared with presymptomatic mutation carriers were further evaluated in a cohort of 17 patients with sporadic FTD, 13 patients with sporadic Alzheimer's disease (AD) and 10 healthy controls (HCs) of similar age. RESULTS: In the GENFI cohort, miR-204-5p and miR-632 were significantly decreased in symptomatic compared with presymptomatic mutation carriers. Decrease of miR-204-5p and miR-632 revealed receiver operator characteristics with an area of 0.89 (90% CI 0.79 to 0.98) and 0.81 (90% CI 0.68 to 0.93), respectively, and when combined an area of 0.93 (90% CI 0.87 to 0.99). In sporadic FTD, only miR-632 was significantly decreased compared with AD and HCs. Decrease of miR-632 revealed an area of 0.90 (90% CI 0.81 to 0.98). CONCLUSIONS: Exosomal miR-204-5p and miR-632 have potential as diagnostic biomarkers for genetic FTD and miR-632 also for sporadic FTD.
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherBMJ
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectGenetic FTD Initiative (GENFI)
dc.subjectHumans
dc.subjecttau Proteins
dc.subjectMicroRNAs
dc.subjectDown-Regulation
dc.subjectFemale
dc.subjectMale
dc.subjectExosomes
dc.subjectFrontotemporal Dementia
dc.subjectBiomarkers
dc.titleDownregulation of exosomal miR-204-5p and miR-632 as a biomarker for FTD: a GENFI study.
dc.typeArticle
prism.endingPage858
prism.issueIdentifier8
prism.publicationDate2018
prism.publicationNameJ Neurol Neurosurg Psychiatry
prism.startingPage851
prism.volume89
dc.identifier.doi10.17863/CAM.22968
dc.identifier.doi10.17863/CAM.22968
dcterms.dateAccepted2018-01-14
rioxxterms.versionofrecord10.1136/jnnp-2017-317492
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2018-08
dc.contributor.orcidSchneider, Raphael [0000-0003-1776-2418]
dc.identifier.eissn1468-330X
rioxxterms.typeJournal Article/Review
pubs.funder-project-idWellcome Trust (103838/Z/14/Z)
pubs.funder-project-idMedical Research Council (MR/J009482/1)
pubs.funder-project-idMedical Research Council (MC_U105597119)
pubs.funder-project-idMedical Research Council (MC_UU_00005/12)
cam.issuedOnline2018-02-06


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International