Design, implementation, and interpretation of amplification studies for prion detection

Nicholas J. Haley, Jürgen A. Richt, Kristen A. Davenport, Davin M. Henderson, Edward A. Hoover, Matteo Manca, Byron Caughey, Douglas Marthaler, Jason C. Bartz, Sabine Gilch

Research output: Contribution to journalArticle

Abstract

Amplification assays for transmissible spongiform encephalopathies have been in development for close to 15 years, with critical implications for the postmortem and antemortem diagnosis of human and animal prion diseases. Little has been published regarding the structured development, implementation and interpretation of experiments making use of protein misfolding cyclic amplification (PMCA) and real time quaking-induced conversion (RT-QuIC), and our goal with this Perspectives manuscript is to offer a framework which might allow for more efficient expansion of pilot studies into diagnostic trials in both human and animal subjects. This framework is made up of approaches common to diagnostic medicine, including a thorough understanding of analytical and diagnostic sensitivity and specificity, an a priori development of amplification strategy, and an effective experimental design. It is our hope that a structured framework for prion amplification assays will benefit not only experiments seeking to sensitively detect naturally-occurring cases of prion diseases and describe the pathogenesis of TSEs, but ultimately assist with future endeavors seeking to use these methods more broadly for other protein misfolding disorders, including Alzheimer's and Parkinson's disease.

Original languageEnglish (US)
Pages (from-to)1-10
Number of pages10
JournalPrion
DOIs
StateAccepted/In press - Mar 8 2018

Fingerprint

Prion Diseases
Prions
Amplification
Hope
Proteostasis Deficiencies
Assays
Animal Diseases
Animals
Manuscripts
Parkinson Disease
Alzheimer Disease
Research Design
Medicine
Design of experiments
Sensitivity and Specificity
Proteins
Experiments

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Infectious Diseases

Cite this

Haley, N. J., Richt, J. A., Davenport, K. A., Henderson, D. M., Hoover, E. A., Manca, M., ... Gilch, S. (Accepted/In press). Design, implementation, and interpretation of amplification studies for prion detection. Prion, 1-10. https://doi.org/10.1080/19336896.2018.1443000

Design, implementation, and interpretation of amplification studies for prion detection. / Haley, Nicholas J.; Richt, Jürgen A.; Davenport, Kristen A.; Henderson, Davin M.; Hoover, Edward A.; Manca, Matteo; Caughey, Byron; Marthaler, Douglas; Bartz, Jason C.; Gilch, Sabine.

In: Prion, 08.03.2018, p. 1-10.

Research output: Contribution to journalArticle

Haley, NJ, Richt, JA, Davenport, KA, Henderson, DM, Hoover, EA, Manca, M, Caughey, B, Marthaler, D, Bartz, JC & Gilch, S 2018, 'Design, implementation, and interpretation of amplification studies for prion detection', Prion, pp. 1-10. https://doi.org/10.1080/19336896.2018.1443000
Haley NJ, Richt JA, Davenport KA, Henderson DM, Hoover EA, Manca M et al. Design, implementation, and interpretation of amplification studies for prion detection. Prion. 2018 Mar 8;1-10. https://doi.org/10.1080/19336896.2018.1443000
Haley, Nicholas J. ; Richt, Jürgen A. ; Davenport, Kristen A. ; Henderson, Davin M. ; Hoover, Edward A. ; Manca, Matteo ; Caughey, Byron ; Marthaler, Douglas ; Bartz, Jason C. ; Gilch, Sabine. / Design, implementation, and interpretation of amplification studies for prion detection. In: Prion. 2018 ; pp. 1-10.
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