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Prion Diseases pp 173-181 | Cite as

Detection and Diagnosis of Prion Diseases Using RT-QuIC: An Update

  • Byron CaugheyEmail author
  • Christina D. Orru
  • Bradley R. Groveman
  • Matilde Bongianni
  • Andrew G. Hughson
  • Lynne D. Raymond
  • Matteo Manca
  • Allison Kraus
  • Gregory J. Raymond
  • Michele Fiorini
  • Maurizio Pocchiari
  • Gianluigi Zanusso
Protocol
  • 429 Downloads
Part of the Neuromethods book series (NM, volume 129)

Abstract

Until recently, it has been difficult to detect all infectious levels of prions and diagnose prion diseases in living humans and other animals. Real-time quaking-induced conversion (RT-QuIC), an ultrasensitive test based on amplification of the amyloid seeding activity of prions, is now achieving the sensitivity and practicality required for routine diagnostics. Adaptations and refinements of RT-QuIC assays currently allow the detection of most of the known prion diseases of mammals, often with sensitivities that are greater than those of animal bioassays. Many tissues and fluids have been shown to be suitable for RT-QuIC analysis. The most significant and extensively validated application is its use in diagnosing sporadic Creutzfeldt–Jakob disease (sCJD) using cerebrospinal fluid. Recent progress with this test has improved diagnostic sensitivities up to 96% with assays that take less than 24 h. Moreover, as tests of a disease-specific marker, RT-QuIC assays have repeatedly demonstrated specificities of 98–100%. Other diagnostic specimens, such as nasal brushings, have shown even higher sensitivity and specificity, but have not been as extensively evaluated. These tests have already shown considerable potential to provide definitive antemortem diagnosis of sCJD, but further testing is required for full validation. Step-by-step RT-QuIC protocols will soon be published elsewhere, so here we provide updates on the range of RT-QuIC tests for prions as well as some additional practical tips on performing and optimizing various RT-QuIC applications.

Key words

RT-QuIC Prion Diagnosis Cerebrospinal fluid Nasal swab Creutzfeldt–Jakob disease Seed 

Notes

Acknowledgments

This work was supported in part by the Intramural Research Program of the NIAID.

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Copyright information

© Springer Science+Business Media LLC 2017

Authors and Affiliations

  • Byron Caughey
    • 1
    Email author
  • Christina D. Orru
    • 1
  • Bradley R. Groveman
    • 1
  • Matilde Bongianni
    • 2
  • Andrew G. Hughson
    • 1
  • Lynne D. Raymond
    • 1
  • Matteo Manca
    • 1
  • Allison Kraus
    • 1
  • Gregory J. Raymond
    • 1
  • Michele Fiorini
    • 2
  • Maurizio Pocchiari
    • 3
  • Gianluigi Zanusso
    • 2
  1. 1.Laboratory of Persistent Viral Diseases, Rocky Mountain LaboratoriesNational Institute for Allergy and Infectious Diseases, National Institutes of HealthHamiltonUSA
  2. 2.Department of Neurological and Movement SciencesUniversity of VeronaVeronaItaly
  3. 3.Department of Cell Biology and NeurosciencesIstituto Superiore di SanitàRomeItaly

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