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Detection of prions in matching post-mortem skin and cerebrospinal fluid samples using second-generation real-time quaking-induced conversion assay

S. Baranová, T. Moško, M. Brůžová, T. Haldiman, C. Kim, JG. Safar, R. Matěj, K. Holada

. 2024 ; 14 (1) : 6294. [pub] 20240315

Language English Country England, Great Britain

Document type Journal Article

Persistent link   https://www.medvik.cz/link/bmc24006716

Grant support
R01 NS074317 NINDS NIH HHS - United States

Real-time quaking-induced conversion assay (RT-QuIC) exploits templating activity of pathogenic prion protein for ultrasensitive detection of prions. We have utilized second generation RT-QuIC assay to analyze matching post-mortem cerebrospinal fluid and skin samples of 38 prion disease patients and of 30 deceased neurological controls. The analysis of cerebrospinal fluid samples led to 100% sensitivity and 100% specificity, but some samples had to be diluted before the analysis to alleviate the effect of present RT-QuIC inhibitors. The analysis of the corresponding skin samples provided 89.5% sensitivity and 100% specificity. The median seeding dose present in the skin was one order of magnitude higher than in the cerebrospinal fluid, despite the overall fluorescent signal of the skin samples was comparatively lower. Our data support the use of post-mortem cerebrospinal fluid for confirmation of prion disease diagnosis and encourage further studies of the potential of skin biopsy samples for intra-vitam prion diseases ́ diagnostics.

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$a Moško, Tibor $u Institute of Immunology and Microbiology, First Faculty of Medicine, Charles University, Prague, Czech Republic
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$a Brůžová, Magdalena $u Department of Pathology and Molecular Medicine, Third Faculty of Medicine, Charles University and Thomayer University Hospital, Prague, Czech Republic
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$a Haldiman, Tracy $u Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, 44106, USA $u Department Neurology, Case Western Reserve University School of Medicine, Cleveland, OH, 44106, USA
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$a Kim, Chae $u Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, 44106, USA $u Department Neurology, Case Western Reserve University School of Medicine, Cleveland, OH, 44106, USA
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$a Matěj, Radoslav $u Department of Pathology and Molecular Medicine, Third Faculty of Medicine, Charles University and Thomayer University Hospital, Prague, Czech Republic $u Department of Pathology, Third Faculty of Medicine, Charles University and University Hospital Kralovske Vinohrady, Prague, Czech Republic $u Department of Pathology, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic
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