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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

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, Wen-Quan Zou

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. More... »

PAGES

247

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41467-018-08130-9

DOI

http://dx.doi.org/10.1038/s41467-018-08130-9

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1111348239

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30651538


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