Cerebrospinal Fluid Prion Disease Biomarkers in Pre-clinical and Clinical Naturally Occurring Scrapie
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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.
KeywordsScrapie Cerebrospinal fluid Prion disease Biomarkers Prion protein 14-3-3 protein Tau protein
We thank Nadine Gotzmann, Silja Koechy, and Sonia Gómez for technical assistance.
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.
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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