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Cerebrospinal Fluid Prion Disease Biomarkers in Pre-clinical and Clinical Naturally Occurring Scrapie

  • Franc Llorens
  • Tomás Barrio
  • Ângela Correia
  • Anna Villar-Piqué
  • Katrin Thüne
  • Peter Lange
  • Juan José Badiola
  • Matthias Schmitz
  • Ingolf Lachmann
  • Rosa Bolea
  • Inga Zerr
Article

Abstract

The analysis of the cerebrospinal fluid (CSF) biomarkers in patients with suspected prion diseases became a useful tool in diagnostic routine. Prion diseases can only be identified at clinical stages when the disease already spread throughout the brain and massive neuronal damage occurs. Consequently, the accuracy of CSF tests detecting non-symptomatic patients is unknown. Here, we aimed to investigate the usefulness of CSF-based diagnostic tests in pre-clinical and clinical naturally occurring scrapie. While decreased total prion protein (PrP) levels and positive PrP seeding activity were already detectable at pre-symptomatic stages, the surrogate markers of neuronal damage total tau (tau) and 14-3-3 proteins were exclusively increased at clinical stages. The present findings confirm that alterations in PrP levels and conformation are primary events in the pathology of prion diseases preceding neuronal damage. Our work also supports the potential use of these tests in the screening of pre-symptomatic scrapie and human prion disease cases.

Keywords

Scrapie Cerebrospinal fluid Prion disease Biomarkers Prion protein 14-3-3 protein Tau protein 

Notes

Acknowledgements

We thank Nadine Gotzmann, Silja Koechy, and Sonia Gómez for technical assistance.

Authors’ Contributions

Study conception and design: FL, RB, IZ. Project supervision: FL. Data collection: FL, TB, AC, AV-P, KT, PL, J-JB, MS, RB. Assay development and technical expertise: IL. Data analysis and interpretation: FL, TB, RB, IZ. Drafting the article: FL, TB, RB. Final approval of the version to be published: all authors.

Funding

This study was funded by Robert Koch Institute through funds from the Federal Ministry of Health of Germany (grant no. 1369-341) and DZNE to IZ; by the Spanish Ministry of Health, Instituto Carlos III/Fondo Social Europeo (CP16/00041) to FL; by the Red Nacional de priones (AGL2015-71764-REDT-MINECO) to FL, IZ, RB, and JJB; and by the Spanish Ministry of Economy (grant no. AGL2015-65560-R) to RB. TB was supported by a research grant from the Spanish Ministry of Education and Science (FPU14/04348). This project has been funded at 65% by the Fondo Europeo de Desarrollo Regional (FEDER) through the Interreg V-A España-Francia-Andorra (POCTEFA 2014-2020) programme. AV-P is funded by a Dorothea Schlözer Scholarship (Georg August University – Göttingen).

Compliance with Ethical Standards

Conflict of Interest

Dr. Lachmann reports he is the employer of AJ Roboscreen GmbH, Leipzig, Germany. No other conflict of interest is reported.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Franc Llorens
    • 1
    • 2
    • 3
  • Tomás Barrio
    • 4
    • 5
  • Ângela Correia
    • 3
  • Anna Villar-Piqué
    • 3
  • Katrin Thüne
    • 3
    • 6
  • Peter Lange
    • 3
  • Juan José Badiola
    • 4
    • 5
  • Matthias Schmitz
    • 3
    • 6
  • Ingolf Lachmann
    • 7
  • Rosa Bolea
    • 4
    • 5
  • Inga Zerr
    • 3
    • 6
  1. 1.CIBERNED (Network Centre for Biomedical Research of Neurodegenerative Diseases)Institute Carlos III, Ministry of Health, L’Hospitalet de LlobregatBarcelonaSpain
  2. 2.IDIBELL, Bellvitge Biomedical Research Institute L’Hospitalet de LlobregatBarcelonaSpain
  3. 3.Department of NeurologyUniversity Medical CenterGöttingenGermany
  4. 4.Centro de Encefalopatías y Enfermedades Transmisibles Emergentes (CEETE), Veterinary Faculty, Instituto Agroalimentario de Aragón- IA2Universidad de Zaragoza-CITAZaragozaSpain
  5. 5.Instituto de Investigación Sanitaria de Aragón (IIS)ZaragozaSpain
  6. 6.German Centre for Neurodegenerative Diseases (DZNE)GöttingenGermany
  7. 7.AJ Roboscreen GmbHLeipzigGermany

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