Cystatin F is a biomarker of prion pathogenesis in mice

• Published in: PloS one 2017-02, Vol.12 (2), p.e0171923-e0171923
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Animal models; Animals; Bioindicators; Biology and Life Sciences; Biomarkers; Biotechnology; Bovine spongiform encephalopathy; Brain; Brain - metabolism; Brain - pathology; BSE; Cerebrospinal fluid; Creutzfeldt-Jakob disease; Cystatins; Cystatins - cerebrospinal fluid; Cystatins - genetics; Cystatins - metabolism; Diagnosis; Diagnostic systems; Diagnostic tests; Disease control; Diseases; Enzyme-Linked Immunosorbent Assay; Epidemiology; Ethics; Gene Expression; Gene Expression Profiling; Genetic aspects; Genetically modified mice; Hospitals; Humans; Immunohistochemistry; Male; Medical diagnosis; Medicine and Health Sciences; Messenger RNA; Mice; Neurodegeneration; Neurology; Neuropathology; Parenchyma; Pathogenesis; Prion diseases; Prion Diseases - cerebrospinal fluid; Prion Diseases - genetics; Prion Diseases - metabolism; Prion Diseases - pathology; Prion protein; Prions; Protein folding; Proteins; Research and Analysis Methods; RNA, Messenger - genetics; RNA, Messenger - metabolism; Scrapie; Transcription; Transcription (Genetics)
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0171923

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.