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Nat Commun. 2019 Jan 16;10(1):247. doi: 10.1038/s41467-018-08130-9.

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

Author information

1
Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, 44106, OH, USA.
2
Department of Neurology, The First Hospital of Jilin University, Changchun, 130021, Jilin Province, The People's Republic of China.
3
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Hamilton, 59840, MT, USA.
4
National Prion Disease Pathology Surveillance Center, Case Western Reserve University School of Medicine, Cleveland, 44106, OH, USA.
5
Department of Otolaryngology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shanxi Province, The People's Republic of China.
6
Department of Biochemistry, Virginia Polytechnic Institute and State University, Blacksburg, 24061, Virginia, USA.
7
Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, 44106, OH, USA.
8
Foundational Sciences, Central Michigan University College of Medicine, Mount Pleasant, 48859, MI, USA.
9
State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, The People's Republic of China.
10
Department of Neurology, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, 44106, OH, USA.
11
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Hamilton, 59840, MT, USA. bcaughey@nih.gov.
12
Department of Neurology, The First Hospital of Jilin University, Changchun, 130021, Jilin Province, The People's Republic of China. chuili1967@126.com.
13
Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, 44106, OH, USA. qxk2@case.edu.
14
National Prion Disease Pathology Surveillance Center, Case Western Reserve University School of Medicine, Cleveland, 44106, OH, USA. qxk2@case.edu.
15
Department of Neurology, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, 44106, OH, USA. qxk2@case.edu.
16
National Center for Regenerative Medicine, Case Western Reserve University School of Medicine, Cleveland, 44106, OH, USA. qxk2@case.edu.
17
Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, 44106, OH, USA. wxz6@case.edu.
18
Department of Neurology, The First Hospital of Jilin University, Changchun, 130021, Jilin Province, The People's Republic of China. wxz6@case.edu.
19
National Prion Disease Pathology Surveillance Center, Case Western Reserve University School of Medicine, Cleveland, 44106, OH, USA. wxz6@case.edu.
20
State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, The People's Republic of China. wxz6@case.edu.
21
Department of Neurology, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, 44106, OH, USA. wxz6@case.edu.
22
National Center for Regenerative Medicine, Case Western Reserve University School of Medicine, Cleveland, 44106, OH, USA. wxz6@case.edu.

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.

PMID:
30651538
PMCID:
PMC6335425
DOI:
10.1038/s41467-018-08130-9
[Indexed for MEDLINE]
Free PMC Article

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