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Downregulation of e...
Downregulation of exosomal miR-204-5p and miR-632 as a biomarker for FTD: a GENFI study
- Article/chapterEnglish2018
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LIBRIS-ID:oai:prod.swepub.kib.ki.se:139022406
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http://kipublications.ki.se/Default.aspx?queryparsed=id:139022406URI
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https://doi.org/10.1136/jnnp-2017-317492DOI
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Language:English
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Summary in:English
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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.MethodsGENFI 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.ResultsIn 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).ConclusionsExosomal miR-204-5p and miR-632 have potential as diagnostic biomarkers for genetic FTD and miR-632 also for sporadic FTD.
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McKeever, P
(author)
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Kim, T
(author)
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Graff, CKarolinska Institutet
(author)
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van Swieten, JC
(author)
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Karydas, A
(author)
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Boxer, A
(author)
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Rosen, H
(author)
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Miller, BL
(author)
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Laforce, R
(author)
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Galimberti, D
(author)
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Masellis, M
(author)
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Borroni, B
(author)
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Zhang, ZL
(author)
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Zinman, L
(author)
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Rohrer, JD
(author)
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Tartaglia, MC
(author)
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Robertson, J
(author)
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Karolinska Institutet
(creator_code:org_t)
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In:Journal of neurology, neurosurgery, and psychiatry: BMJ89:8, s. 851-8581468-330X0022-3050
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Schneider, R
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McKeever, P
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Kim, T
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Graff, C
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van Swieten, JC
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Karydas, A
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Boxer, A
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Rosen, H
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Miller, BL
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Laforce, R
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Galimberti, D
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Masellis, M
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Borroni, B
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Zhang, ZL
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Zinman, L
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Rohrer, JD
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Tartaglia, MC
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Robertson, J
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Karolinska Institutet