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Real time quaking-induced conversion analysis of cerebrospinal fluid in sporadic Creutzfeldt–Jakob disease

Authors

  • Lynne I. McGuire PhD,

    1. National Creutzfeldt–Jakob Disease Research & Surveillance Unit, University of Edinburgh, Edinburgh, United Kingdom
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  • Alexander H. Peden PhD,

    1. National Creutzfeldt–Jakob Disease Research & Surveillance Unit, University of Edinburgh, Edinburgh, United Kingdom
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  • Christina D. Orrú PhD,

    1. Laboratory of Persistent Viral Disease, National Institute of Allergy and Infectious Diseases Rocky Mountain Laboratories, National Institutes of Health, Hamilton, Montana, United States of America
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  • Jason M. Wilham PhD,

    1. Laboratory of Persistent Viral Disease, National Institute of Allergy and Infectious Diseases Rocky Mountain Laboratories, National Institutes of Health, Hamilton, Montana, United States of America
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  • Nigel E. Appleford Cbiol,

    1. Bristol Institute for Transfusion Sciences, National Health Service Blood and Transplant, Bristol, United Kingdom
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  • Gary Mallinson PhD,

    1. Bristol Institute for Transfusion Sciences, National Health Service Blood and Transplant, Bristol, United Kingdom
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  • Mary Andrews BSc,

    1. National Creutzfeldt–Jakob Disease Research & Surveillance Unit, University of Edinburgh, Edinburgh, United Kingdom
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  • Mark W. Head PhD,

    1. National Creutzfeldt–Jakob Disease Research & Surveillance Unit, University of Edinburgh, Edinburgh, United Kingdom
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  • Byron Caughey PhD,

    1. Laboratory of Persistent Viral Disease, National Institute of Allergy and Infectious Diseases Rocky Mountain Laboratories, National Institutes of Health, Hamilton, Montana, United States of America
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  • Robert G. Will FRCP,

    1. National Creutzfeldt–Jakob Disease Research & Surveillance Unit, University of Edinburgh, Edinburgh, United Kingdom
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  • Richard S. G. Knight FRCP,

    1. National Creutzfeldt–Jakob Disease Research & Surveillance Unit, University of Edinburgh, Edinburgh, United Kingdom
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  • Alison J. E. Green PhD

    Corresponding author
    1. National Creutzfeldt–Jakob Disease Research & Surveillance Unit, University of Edinburgh, Edinburgh, United Kingdom
    • The National CJD Research & Surveillance Unit, University of Edinburgh, Western General Hospital, Edinburgh, EH4 2XU United Kingdom
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Abstract

Objective:

Current cerebrospinal fluid (CSF) tests for sporadic Creutzfeldt–Jakob disease (sCJD) are based on the detection of surrogate markers of neuronal damage such as CSF 14-3-3, which are not specific for sCJD. A number of prion protein conversion assays have been developed, including real time quaking-induced conversion (RT-QuIC). The objective of this study is to investigate whether CSF RT-QuIC analysis could be used as a diagnostic test in sCJD.

Methods:

An exploratory study was undertaken that analyzed 108 CSF samples from patients with neuropathologically confirmed sCJD or from control patients. Of the 108 CSF samples, 56 were from sCJD patients (30 female, 26 male; aged 31–84 years; mean age, 62.3 ± 13.5 years), and 52 were from control patients (26 female, 26 male; aged 43–84 years; mean age, 67.8 ± 10.4 years). A confirmatory group of 118 patients was subsequently examined that consisted of 67 cases of neuropathologically confirmed sCJD (33 female, 34 male; aged 39–82 years; mean age, 67.5 ± 9.0 years) and 51 control cases (26 female, 25 male; aged 36–87 years; mean age, 63.5 ± 11.6 years).

Results:

The exploratory study showed that RT-QuIC analysis had a sensitivity of 91% and a specificity of 98% for the diagnosis of sCJD. These results were confirmed in the confirmatory study, which showed that CSF RT-QuIC analysis had a sensitivity and specificity of 87% and 100%, respectively.

Interpretation:

This study shows that CSF RT-QuIC analysis has the potential to be a more specific diagnostic test for sCJD than current CSF tests. ANN NEUROL 2012;72:278–285.

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