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  • Patil, Ketan S. (author)

Combinatory microRNA serum signatures as classifiers of Parkinson's disease

  • Article/chapterEnglish2019

Publisher, publication year, extent ...

  • Elsevier,2019
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:umu-164077
  • https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-164077URI
  • https://doi.org/10.1016/j.parkreldis.2019.04.010DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:141934186URI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Introduction: As current clinical diagnostic protocols for Parkinson's disease (PD) may be prone to inaccuracies there is a need to identify and validate molecular biomarkers, such as circulating microRNAs, which will complement current practices and increase diagnostic accuracy. This study identifies, verifies and validates combinatory serum microRNA signatures as diagnostic classifiers of PD across different patient cohorts. Methods: 370 PD (drug naive) and control serum samples from the Norwegian ParkWest study were used for identification and verification of differential microRNA levels in PD which were validated in a blind study using 64 NY Parkinsonism in UMea (NYPUM) study serum samples and tested for specificity in 48 Dementia Study of Western Norway (DemWest) study Alzheimer's disease (AD) serum samples using miRNA-microarrays, and quantitative (q) RT-PCR. Proteomic approaches identified potential molecular targets for these microRNAs. Results: Using Affymetrix GeneChip (R) miRNA 4.0 arrays and qRT-PCR we comprehensively analyzed serum microRNA levels and found that the microRNA (PARKmiR)-combinations, hsa-miR-335-5p/hsa-miR-3613-3p (95% CI, 0.87-0.94), hsa-miR-335-5p/hsa-miR-6865-3p (95% CI, 0.87-0.93), and miR-335-5p/miR-3613-3p/miR-6865-3p (95% CI, 0.87-0.94) show a high degree of discriminatory accuracy (AUC 0.9-1.0). The PARKmiR signatures were validated in an independent PD cohort (AUC <= 0.71) and analysis in AD serum samples showed PARKmiR signature specificity to PD. Proteomic analyses showed that the PAFtKmiRs regulate key PD-associated proteins, including alpha-synuclein and Leucine Rich Repeat Kinase 2. Conclusions: Our study has identified and validated unique miRNA serum signatures that represent PD classifiers, which may complement and increase the accuracy of current diagnostic protocols.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Basak, Indranil (author)
  • Dalen, Ingvild (author)
  • Hoedt, Esthelle (author)
  • Lange, Johannes (author)
  • Lunde, Kristin A. (author)
  • Liu, Ying (author)
  • Tysnes, Ole-Bjørn (author)
  • Forsgren, LarsUmeå universitet,Klinisk neurovetenskap(Swepub:umu)lafo0001 (author)
  • Aarsland, DagKarolinska Institutet (author)
  • Neubert, Thomas A. (author)
  • Larsen, Jan Petter (author)
  • Alves, Guido (author)
  • Møller, Simon Geir (author)
  • Umeå universitetKlinisk neurovetenskap (creator_code:org_t)

Related titles

  • In:Parkinsonism & Related Disorders: Elsevier64, s. 202-2101353-80201873-5126

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