Early Detection of Abnormal Prion Protein in Genetic Human Prion Diseases Now Possible Using Real-Time QUIC Assay

• Sano, Kazunori

• Satoh, Katsuya

• Atarashi, Ryuichiro

• Takashima, Hiroshi

• Iwasaki, Yasushi

• Yoshida, Mari

• Sanjo, Nobuo

• Murai, Hiroyuki

• Mizusawa, Hidehiro

• Schmitz, Matthias

• Zerr, Inga

• Kim, Yong-Sun

• Nishida, Noriyuki

• Andrew Francis Hill

  editor

Abstract

Introduction: The definitive diagnosis of genetic prion diseases (gPrD) requires pathological confirmation. To date, diagnosis has relied upon the finding of the biomarkers 14-3-3 protein and total tau (t-tau) protein in the cerebrospinal fluid (CSF), but many researchers have reported that these markers are not sufficiently elevated in gPrD, especially in Gerstmann-Sträussler-Scheinker syndrome (GSS). We recently developed a new in vitro amplification technology, designated "real-time quaking-induced conversion (RT-QUIC)", to detect the abnormal form of prion protein in CSF from sporadic Creutzfeldt-Jakob disease (sCJD) patients. In the present study, we aimed to investigate the presence of biomarkers and evaluate RT-QUIC assay in patients with gPrD, as the utility of RT-QUIC as a diagnostic tool in gPrD has yet to be determined. Method/Principal Findings: 56 CSF samples were obtained from gPrD patients, including 20 cases of GSS with P102L mutation, 12 cases of fatal familial insomnia (FFI; D178N), and 24 cases of genetic CJD (gCJD), comprising 22 cases with E200K mutation and 2 with V203I mutation. We subjected all CSF samples to RT-QUIC assay, analyzed 14-3-3 protein by Western blotting, and measured t-tau protein using an ELISA kit. The detection sensitivities of RT-QUIC were as follows: GSS (78%), FFI (100%), gCJD E200K (87%), and gCJD V203I (100%). On the other hand the detection sensitivities of biomarkers were considerably lower: GSS (11%), FFI (0%), gCJD E200K (73%), and gCJD V203I (67%). Thus, RT-QUIC had a much higher detection sensitivity compared with testing for biomarkers, especially in patients with GSS and FFI. Conclusion/Significance: RT-QUIC assay is more sensitive than testing for biomarkers in gPrD patients. RT-QUIC method would thus be useful as a diagnostic tool when the patient or the patient's family does not agree to genetic testing, or to confirm the diagnosis in the presence of a positive result for genetic testing.

PLoS ONE, 8(1), e54915; 2013

Journal

• PLoS ONE

  PLoS ONE 8 (1), e54915-, 2013-01-25

  Public Library of Science

Keywords

• Multidisciplinary

Details

• CRID: 1050568772228567168
• NII Article ID: 120006985758
• ISSN: 19326203
• DOI: 10.1371/journal.pone.0054915
• HANDLE: 10069/31488
• Web Site: https://nagasaki-u.repo.nii.ac.jp/records/8699
• Web Site: http://dx.plos.org/10.1371/journal.pone.0054915
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • Crossref
  • CiNii Articles
  • KAKEN