@article{ea9175bbd629459f89fb6377b1eb68c6,
title = "Early preclinical detection of prions in the skin of prion-infected animals",
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.",
author = "Zerui Wang and Matteo Manca and Aaron Foutz and Camacho, {Manuel V.} and Raymond, {Gregory J.} and Brent Race and Orru, {Christina D.} and Jue Yuan and Pingping Shen and Baiya Li and Yue Lang and Johnny Dang and Alise Adornato and Katie Williams and Maurer, {Nicholas R.} and Pierluigi Gambetti and Bin Xu and Witold Surewicz and Petersen, {Robert B.} and Xiaoping Dong and Appleby, {Brian S.} and Byron Caughey and Li Cui and Qingzhong Kong and Zou, {Wen Quan}",
note = "Funding Information: We thank Miriam Warren and Diane Kofskey for skillful histologic and immunohistochemical preparations. We thank Andrew Hughson (RML) for providing recombinant hamster prion protein. Supported by the CJD Foundation and the National Institutes of Health (NIH) NS062787 and NS087588 to W.-Q.Z., NS062787 and NS109532 to W.-Q. Z., and Q.K., NS088604 to Q.K., the Intramural Research Program of the NIAID, NIH to B.C., the Centers for Disease Control and Prevention Contract UR8/CCU515004 to B.S.A. as well as the National Natural Science Foundation of China (No. 81671186) to L.C. Publisher Copyright: {\textcopyright} 2019, The Author(s).",
year = "2019",
month = dec,
day = "1",
doi = "10.1038/s41467-018-08130-9",
language = "English",
volume = "10",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Communications",
number = "1",
}