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

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dc.contributor.authorWang, Zeruien
dc.contributor.authorManca, Matteoen
dc.contributor.authorFoutz, Aaronen
dc.contributor.authorCamacho, Manuel V.en
dc.contributor.authorRaymond, Gregory J.en
dc.contributor.authorRace, Brenten
dc.contributor.authorOrru, Christina D.en
dc.contributor.authorYuan, Jueen
dc.contributor.authorShen, Pingpingen
dc.contributor.authorLi, Baiyaen
dc.contributor.authorLang, Yueen
dc.contributor.authorDang, Johnnyen
dc.contributor.authorAdornato, Aliseen
dc.contributor.authorWilliams, Katieen
dc.contributor.authorMaurer, Nicholas R.en
dc.contributor.authorGambetti, Pierluigien
dc.contributor.authorXu, Binen
dc.contributor.authorSurewicz, Witolden
dc.contributor.authorPetersen, Robert B.en
dc.contributor.authorDong, Xiaopingen
dc.contributor.authorAppleby, Brian S.en
dc.contributor.authorCaughey, Byronen
dc.contributor.authorCui, Lien
dc.contributor.authorKong, Qingzhongen
dc.contributor.authorZou, Wen-Quanen
dc.contributor.departmentBiochemistryen
dc.date.accessioned2019-02-06T18:07:41Zen
dc.date.available2019-02-06T18:07:41Zen
dc.date.issued2019-01-16en
dc.description.abstractA 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.en
dc.description.notesWe 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.en
dc.description.sponsorshipCJD Foundationen
dc.description.sponsorshipNational Institutes of Health (NIH) [NS062787, NS087588, NS109532, NS088604]en
dc.description.sponsorshipIntramural Research Program of the NIAID, NIHen
dc.description.sponsorshipCenters for Disease Control and Prevention [UR8/CCU515004]en
dc.description.sponsorshipNational Natural Science Foundation of China [81671186]en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1038/s41467-018-08130-9en
dc.identifier.issn2041-1723en
dc.identifier.other247en
dc.identifier.pmid30651538en
dc.identifier.urihttp://hdl.handle.net/10919/87474en
dc.identifier.volume10en
dc.language.isoenen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleEarly preclinical detection of prions in the skin of prion-infected animalsen
dc.title.serialNature Communicationsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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