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Protein Misfolding Cyclic Amplification of Prions
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Prion protein amplification techniques.

Alison J E Green1, Gianluigi Zanusso2

  • 1National CJD Research and Surveillance Unit, University of Edinburgh, Edinburgh, United Kingdom.

Handbook of Clinical Neurology
|June 12, 2018
PubMed
Summary
This summary is machine-generated.

Protein amplification assays like PMCA and RT-QuIC detect prion diseases by amplifying misfolded prion protein (PrPTSE). RT-QuIC is highly effective for diagnosing sporadic Creutzfeldt-Jakob disease (sCJD) via cerebrospinal fluid.

Keywords:
PrP(TSE)cerebrospinal fluidgenetic CJDhuman prion diseasesiatrogenicolfactory mucosaprion proteinprotein misfolding cyclic amplificationreal-time quaking-induced conversionsporadic CJDvariant CJD

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Area of Science:

  • Neuroscience
  • Biochemistry
  • Medical Diagnostics

Background:

  • Prion diseases are characterized by misfolded prion protein (PrPTSE) that induces conformational changes in normal prion protein (PrP).
  • Detecting small amounts of PrPTSE in biological samples is challenging but crucial for diagnosing prion diseases.

Purpose of the Study:

  • To review the application and diagnostic utility of protein amplification techniques, specifically Protein Misfolding Cyclic Amplification (PMCA) and Real-Time Quaking-Induced Conversion (RT-QuIC).
  • To highlight the effectiveness of these assays in detecting and differentiating prion diseases, including sporadic and variant Creutzfeldt-Jakob disease (sCJD and vCJD).

Main Methods:

  • Utilizing protein misfolding cyclic amplification (PMCA) and real-time quaking-induced conversion (RT-QuIC) assays.
  • Applying these assays to analyze cerebrospinal fluid (CSF) and other biological samples for the presence of PrPTSE.

Main Results:

  • Cerebrospinal fluid (CSF) RT-QuIC demonstrates high sensitivity and specificity for diagnosing sporadic Creutzfeldt-Jakob disease (sCJD), leading to its inclusion in diagnostic criteria.
  • RT-QuIC is also valuable for diagnosing genetic prion diseases when other CSF tests are negative.
  • PMCA shows promise for diagnosing variant Creutzfeldt-Jakob disease (vCJD) and distinguishing it from sCJD, which is critical given potential new vCJD cases.

Conclusions:

  • Protein amplification assays (PMCA and RT-QuIC) are powerful tools for detecting and diagnosing prion diseases.
  • CSF RT-QuIC is a key diagnostic method for sCJD.
  • PMCA may become essential for identifying vCJD and differentiating it from sCJD in the future.