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

Author

Listed:
  • Zerui Wang

    (Case Western Reserve University School of Medicine
    The First Hospital of Jilin University)

  • 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
    The First Hospital of Jilin University)

  • Baiya Li

    (Case Western Reserve University School of Medicine
    The First Affiliated Hospital of Xi’an Jiaotong University)

  • Yue Lang

    (Case Western Reserve University School of Medicine
    The First Hospital of Jilin University)

  • 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
    Central Michigan University College 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
    Case Western Reserve University School of Medicine
    University Hospitals Cleveland Medical Center, 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
    Case Western Reserve University School of Medicine
    University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine
    Case Western Reserve University School of Medicine)

  • Wen-Quan Zou

    (Case Western Reserve University School of Medicine
    The First Hospital of Jilin University
    Case Western Reserve University School of Medicine
    National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention)

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.

Suggested Citation

  • 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 & Kati, 2019. "Early preclinical detection of prions in the skin of prion-infected animals," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-018-08130-9
    DOI: 10.1038/s41467-018-08130-9
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