Early preclinical detection of prions in the skin of prion-infected animals

Zerui Wang, Matteo Manca, Aaron Foutz, Manuel V. Camacho, Gregory J. Raymond, Brent Race, Christina D. Orru, Jue Yuan, Pingping Shen, Baiya Li, Yue Lang, Johnny Dang, Alise Adornato, Katie Williams, Nicholas R. Maurer, Pierluigi Gambetti, Bin Xu, Witold Surewicz, Robert B. Petersen, Xiaoping Dong, Brian S. Appleby, Byron Caughey (), Li Cui (), Qingzhong Kong () and Wen-Quan Zou ()
Additional contact information
Zerui Wang: Case Western Reserve University School of Medicine
Matteo Manca: National Institutes of Health (NIH)
Aaron Foutz: Case Western Reserve University School of Medicine
Manuel V. Camacho: Case Western Reserve University School of Medicine
Gregory J. Raymond: National Institutes of Health (NIH)
Brent Race: National Institutes of Health (NIH)
Christina D. Orru: National Institutes of Health (NIH)
Jue Yuan: Case Western Reserve University School of Medicine
Pingping Shen: Case Western Reserve University School of Medicine
Baiya Li: Case Western Reserve University School of Medicine
Yue Lang: Case Western Reserve University School of Medicine
Johnny Dang: Case Western Reserve University School of Medicine
Alise Adornato: Case Western Reserve University School of Medicine
Katie Williams: National Institutes of Health (NIH)
Nicholas R. Maurer: Case Western Reserve University School of Medicine
Pierluigi Gambetti: Case Western Reserve University School of Medicine
Bin Xu: Virginia Polytechnic Institute and State University
Witold Surewicz: Case Western Reserve University School of Medicine
Robert B. Petersen: Case Western Reserve University School of Medicine
Xiaoping Dong: National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention
Brian S. Appleby: Case Western Reserve University School of Medicine
Byron Caughey: National Institutes of Health (NIH)
Li Cui: The First Hospital of Jilin University
Qingzhong Kong: Case Western Reserve University School of Medicine
Wen-Quan Zou: Case Western Reserve University School of Medicine

Nature Communications, 2019, vol. 10, issue 1, 1-11

Abstract: Abstract A definitive pre-mortem diagnosis of prion disease depends on brain biopsy for prion detection currently and no validated alternative preclinical diagnostic tests have been reported to date. To determine the feasibility of using skin for preclinical diagnosis, here we report ultrasensitive serial protein misfolding cyclic amplification (sPMCA) and real-time quaking-induced conversion (RT-QuIC) assays of skin samples from hamsters and humanized transgenic mice (Tg40h) at different time points after intracerebral inoculation with 263K and sCJDMM1 prions, respectively. sPMCA detects skin PrPSc as early as 2 weeks post inoculation (wpi) in hamsters and 4 wpi in Tg40h mice; RT-QuIC assay reveals earliest skin prion-seeding activity at 3 wpi in hamsters and 20 wpi in Tg40h mice. Unlike 263K-inoculated animals, mock-inoculated animals show detectable skin/brain PrPSc only after long cohabitation periods with scrapie-infected animals. Our study provides the proof-of-concept evidence that skin prions could be a biomarker for preclinical diagnosis of prion disease.

Date: 2019
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DOI: 10.1038/s41467-018-08130-9

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