Nuvolone, Mario; Schmid, Nicolas; Miele, Gino; Sorce, Silvia; Moos, Rita; Schori, Christian; Beerli, Roger R; Bauer, Monika; Saudan, Philippe; Dietmeier, Klaus; Lachmann, Ingolf; Linnebank, Michael; Martin, Roland; Kallweit, Ulf; Kana, Veronika; Rushing, Elisabeth J; Budka, Herbert; Aguzzi, Adriano (2017). Cystatin F is a biomarker of prion pathogenesis in mice. PLoS ONE, 12(2), e0171923. Public Library of Science 10.1371/journal.pone.0171923
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Misfolding of the cellular prion protein (PrPC) into the scrapie prion protein (PrPSc) results in progressive, fatal, transmissible neurodegenerative conditions termed prion diseases. Experimental and epidemiological evidence point toward a protracted, clinically silent phase in prion diseases, yet there is no diagnostic test capable of identifying asymptomatic individuals incubating prions. In an effort to identify early biomarkers of prion diseases, we have compared global transcriptional profiles in brains from pre-symptomatic prion-infected mice and controls. We identified Cst7, which encodes cystatin F, as the most strongly upregulated transcript in this model. Early and robust upregulation of Cst7 mRNA levels and of its cognate protein was validated in additional mouse models of prion disease. Surprisingly, we found no significant increase in cystatin F levels in both cerebrospinal fluid or brain parenchyma of patients with Creutzfeldt-Jakob disease compared to Alzheimer's disease or non-demented controls. Our results validate cystatin F as a useful biomarker of early pathogenesis in experimental models of prion disease, and point to unexpected species-specific differences in the transcriptional responses to prion infections.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Neurology |
UniBE Contributor: |
Kallweit, Ulf |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1932-6203 |
Publisher: |
Public Library of Science |
Language: |
English |
Submitter: |
Stefanie Hetzenecker |
Date Deposited: |
10 Jan 2018 08:54 |
Last Modified: |
05 Dec 2022 15:08 |
Publisher DOI: |
10.1371/journal.pone.0171923 |
PubMed ID: |
28178353 |
BORIS DOI: |
10.7892/boris.107974 |
URI: |
https://boris.unibe.ch/id/eprint/107974 |
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