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Downregulation of exosomal miR-204-5p and miR-632 as a biomarker for FTD: a GENFI study

Schneider, Raphael, McKeever, Paul, Kim, TaeHyung, Graff, Caroline, van Swieten, John Cornelis, Karydas, Anna, Boxer, Adam, Rosen, Howie, Miller, Bruce L, Laforce Jr, Robert, Galimberti, Daniela, Masellis, Mario, Borroni, Barbara, Zhang, Zhaolei, Zinman, Lorne, Rohrer, Jonathan Daniel, Tartaglia, Maria Carmela, Robertson, Janice·2018·Journal of Neurology, Neurosurgery & Psychiatry
DOI 10.1136/jnnp-2017-317492PMC PMC6045452
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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.

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Metadata

Authors
Schneider, R., McKeever, P., Kim, T., Graff, C., van Swieten, J. C., Karydas, A., Boxer, A., Rosen, H., Miller, B. L., Laforce Jr, R., Galimberti, D., Masellis, M., Borroni, B., Zhang, Z., Zinman, L., Rohrer, J. D., Tartaglia, M. C., & Robertson, J.
ORCID
Schneider, Raphael
Venue
Journal of Neurology, Neurosurgery & Psychiatry
Publisher
BMJ
Published
2018-02-06
Volume
89
Issue
8
Pages
851-858
ISSN
  • 0022-3050
  • 1468-330X
DOI
10.1136/jnnp-2017-317492
PMC
PMC6045452
Cited by
62
References
4
Language
en

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