{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T13:58:21Z","timestamp":1790517501443,"version":"4.1.0"},"reference-count":42,"publisher":"BMJ","issue":"8","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Neurol Neurosurg Psychiatry"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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\u2019s disease (AD) and 10 healthy controls (HCs) of similar age.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Exosomal miR-204-5p and miR-632 have potential as diagnostic biomarkers for genetic FTD and miR-632 also for sporadic FTD.<\/jats:p><\/jats:sec>","DOI":"10.1136\/jnnp-2017-317492","type":"journal-article","created":{"date-parts":[[2018,2,6]],"date-time":"2018-02-06T17:15:40Z","timestamp":1517937340000},"page":"851-858","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":62,"title":["Downregulation of exosomal miR-204-5p and miR-632 as a biomarker for FTD: a GENFI study"],"prefix":"10.1136","volume":"89","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1776-2418","authenticated-orcid":false,"given":"Raphael","family":"Schneider","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"McKeever","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"TaeHyung","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Graff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John Cornelis","family":"van Swieten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Karydas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Boxer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howie","family":"Rosen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce L","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Laforce Jr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Galimberti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Masellis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Borroni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaolei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorne","family":"Zinman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan Daniel","family":"Rohrer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Carmela","family":"Tartaglia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janice","family":"Robertson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2018,2,6]]},"reference":[{"key":"2020050722305591000_89.8.851.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)00461-4"},{"key":"2020050722305591000_89.8.851.2","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1016\/S1474-4422(16)00065-X","article-title":"Epigenetics of dementia: understanding the disease as a transformation rather than a state","volume":"15","author":"Maloney","year":"2016","journal-title":"Lancet Neurol"},{"key":"2020050722305591000_89.8.851.3","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awg204"},{"key":"2020050722305591000_89.8.851.4","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn257"},{"key":"2020050722305591000_89.8.851.5","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1186\/1471-2164-12-527","article-title":"Altered microRNA expression in frontotemporal lobar degeneration with TDP-43 pathology caused by progranulin mutations","volume":"12","author":"Kocerha","year":"2011","journal-title":"BMC Genomics"},{"key":"2020050722305591000_89.8.851.6","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0521-12.2012"},{"key":"2020050722305591000_89.8.851.7","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3965"},{"key":"2020050722305591000_89.8.851.8","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1038\/nrg.2016.134","article-title":"A network-biology perspective of microRNA function and dysfunction in cancer","volume":"17","author":"Bracken","year":"2016","journal-title":"Nat Rev Genet"},{"key":"2020050722305591000_89.8.851.9","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3835(83)90040-X"},{"key":"2020050722305591000_89.8.851.10","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s40169-016-0087-4","article-title":"Horizontal transfer of RNA and proteins between cells by extracellular microvesicles: 14\u00a0years later","volume":"5","author":"Ratajczak","year":"2016","journal-title":"Clin Transl Med"},{"key":"2020050722305591000_89.8.851.11","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0914843107"},{"key":"2020050722305591000_89.8.851.12","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.6476-10.2011"},{"key":"2020050722305591000_89.8.851.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2010.11.004"},{"key":"2020050722305591000_89.8.851.14","doi-asserted-by":"publisher","DOI":"10.1002\/stem.1129"},{"key":"2020050722305591000_89.8.851.15","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.410944"},{"key":"2020050722305591000_89.8.851.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2016.10.009"},{"key":"2020050722305591000_89.8.851.17","doi-asserted-by":"crossref","unstructured":"Gallo A , Tandon M , Alevizos I , et al . The majority of microRNAs detectable in serum and saliva is concentrated in exosomes. PLoS One 2012;7:e30679. doi:10.1371\/journal.pone.0030679","DOI":"10.1371\/journal.pone.0030679"},{"key":"2020050722305591000_89.8.851.18","doi-asserted-by":"crossref","first-page":"23743","DOI":"10.3402\/jev.v3.23743","article-title":"Exosomes provide a protective and enriched source of miRNA for biomarker profiling compared to intracellular and cell-free blood","volume":"3","author":"Cheng","year":"2014","journal-title":"J Extracell Vesicles"},{"key":"2020050722305591000_89.8.851.19","doi-asserted-by":"publisher","DOI":"10.1016\/0022-3956(75)90026-6"},{"key":"2020050722305591000_89.8.851.20","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awr179"},{"key":"2020050722305591000_89.8.851.21","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31821103e6"},{"key":"2020050722305591000_89.8.851.22","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(94)90191-0"},{"key":"2020050722305591000_89.8.851.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.005"},{"key":"2020050722305591000_89.8.851.24","doi-asserted-by":"publisher","DOI":"10.1186\/2051-5960-1-42"},{"key":"2020050722305591000_89.8.851.25","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"2020050722305591000_89.8.851.26","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3485"},{"key":"2020050722305591000_89.8.851.27","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw1092"},{"key":"2020050722305591000_89.8.851.28","doi-asserted-by":"publisher","DOI":"10.1038\/nature11405"},{"key":"2020050722305591000_89.8.851.29","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/16.7.1686"},{"key":"2020050722305591000_89.8.851.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2011.07.021"},{"key":"2020050722305591000_89.8.851.31","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1503\/jpn.150131","article-title":"Progranulin deficiency induces overactivation of WNT5A expression via TNF-\u03b1\/NF-\u03baB pathway in peripheral cells from frontotemporal dementia-linked granulin mutation carriers","volume":"41","author":"Alqu\u00e9zar","year":"2016","journal-title":"J Psychiatry Neurosci"},{"key":"2020050722305591000_89.8.851.32","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn023"},{"key":"2020050722305591000_89.8.851.33","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2016.91"},{"key":"2020050722305591000_89.8.851.34","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.3233\/JAD-140756","article-title":"Circulating miRNAs as potential biomarkers in Alzheimer\u2019s disease","volume":"42","author":"Galimberti","year":"2014","journal-title":"J Alzheimers Dis"},{"key":"2020050722305591000_89.8.851.35","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s40035-016-0053-5","article-title":"miRNA expression profiles in cerebrospinal fluid and blood of patients with Alzheimer\u2019s disease and other types of dementia - an exploratory study","volume":"5","author":"S\u00f8rensen","year":"2016","journal-title":"Transl Neurodegener"},{"key":"2020050722305591000_89.8.851.36","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2011.09.002"},{"key":"2020050722305591000_89.8.851.37","doi-asserted-by":"crossref","unstructured":"Xia Q , Hu Q , Wang H , et al . Induction of COX-2-PGE2 synthesis by activation of the MAPK\/ERK pathway contributes to neuronal death triggered by TDP-43-depleted microglia. Cell Death Dis 2015;6:e1702. doi:10.1038\/cddis.2015.69","DOI":"10.1038\/cddis.2015.69"},{"key":"2020050722305591000_89.8.851.38","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq100"},{"key":"2020050722305591000_89.8.851.39","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2010.09.034"},{"key":"2020050722305591000_89.8.851.40","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-015-1448-6"},{"key":"2020050722305591000_89.8.851.41","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(99)00937-4"},{"key":"2020050722305591000_89.8.851.42","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1326-7-33"}],"container-title":["Journal of Neurology, Neurosurgery &amp; Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jnnp-2017-317492","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,9,25]],"date-time":"2020-09-25T18:09:30Z","timestamp":1601057370000},"score":1,"resource":{"primary":{"URL":"https:\/\/jnnp.bmj.com\/lookup\/doi\/10.1136\/jnnp-2017-317492"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,2,6]]},"references-count":42,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2018,7,12]]},"published-print":{"date-parts":[[2018,8]]}},"alternative-id":["10.1136\/jnnp-2017-317492"],"URL":"https:\/\/doi.org\/10.1136\/jnnp-2017-317492","relation":{},"ISSN":["0022-3050","1468-330X"],"issn-type":[{"value":"0022-3050","type":"print"},{"value":"1468-330X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,2,6]]}}}