eprintid: 10043939
rev_number: 41
eprint_status: archive
userid: 608
dir: disk0/10/04/39/39
datestamp: 2018-02-23 17:08:34
lastmod: 2021-09-19 23:07:04
status_changed: 2019-02-12 16:57:46
type: article
metadata_visibility: show
creators_name: Schneider, R
creators_name: McKeever, P
creators_name: Kim, T
creators_name: Graff, C
creators_name: van Swieten, JC
creators_name: Karydas, A
creators_name: Boxer, A
creators_name: Rosen, H
creators_name: Miller, BL
creators_name: Laforce, R
creators_name: Galimberti, D
creators_name: Masellis, M
creators_name: Borroni, B
creators_name: Zhang, Z
creators_name: Zinman, L
creators_name: Rohrer, JD
creators_name: Tartaglia, MC
creators_name: Robertson, J
creators_name: Genetic FTD Initiative (GENFI), .
title: Downregulation of exosomal miR-204-5p and miR-632 as a biomarker for FTD: a GENFI study
ispublished: pub
divisions: UCL
divisions: B02
divisions: C07
divisions: D07
divisions: F86
note: This is an open access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/.
abstract: OBJECTIVE: 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.
date: 2018-08
date_type: published
official_url: http://doi.org/10.1136/jnnp-2017-317492
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
article_type_text: Article
verified: verified_manual
elements_id: 1535526
doi: 10.1136/jnnp-2017-317492
pii: jnnp-2017-317492
lyricists_name: Bocchetta, Martina
lyricists_name: Rohrer, Jonathan
lyricists_id: MBOCC01
lyricists_id: JDROH34
actors_name: Laslett, David
actors_id: DLASL34
actors_role: owner
full_text_status: public
publication: Journal of Neurology, Neurosurgery & Psychiatry
volume: 89
number: 8
pagerange: 851-858
issn: 1468-330X
citation:        Schneider, R;    McKeever, P;    Kim, T;    Graff, C;    van Swieten, JC;    Karydas, A;    Boxer, A;                                                 ... Genetic FTD Initiative (GENFI), .; + view all <#>        Schneider, R;  McKeever, P;  Kim, T;  Graff, C;  van Swieten, JC;  Karydas, A;  Boxer, A;  Rosen, H;  Miller, BL;  Laforce, R;  Galimberti, D;  Masellis, M;  Borroni, B;  Zhang, Z;  Zinman, L;  Rohrer, JD;  Tartaglia, MC;  Robertson, J;  Genetic FTD Initiative (GENFI), .;   - view fewer <#>    (2018)    Downregulation of exosomal miR-204-5p and miR-632 as a biomarker for FTD: a GENFI study.                   Journal of Neurology, Neurosurgery & Psychiatry , 89  (8)   pp. 851-858.    10.1136/jnnp-2017-317492 <https://doi.org/10.1136/jnnp-2017-317492>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10043939/1/851.full.pdf