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Peer-reviewedCC BY-NCBMJ neurology open

Value of positive RT-QuIC replicate number in sporadic Creutzfeldt-Jakob disease.

  • Matteo Zavarella1
  • Peter Hermann2
  • Susana da Silva Correia2
  • Sezgi Canaslan Eyyuboglu2
  • Matthias Schmitz2
  • Massimo Filippi1,3,4,5,6
  • Inga Zerr2,7
7 affiliations
  1. 1Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
  2. 2National TSE Reference Centre, Department of Neurology, University of Göttingen, Göttingen, Germany.
  3. 3Vita-Salute San Raffaele University, Milan, Italy.
  4. 4Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
  5. 5Neurophysiology Service, IRCCS San Raffaele Scientific Institute, Milan, Italy.
  6. 6Neurorehabilitation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
  7. 7German Center for Neurodegenerative Diseases (DZNE), University of Göttingen, Göttingen, Germany.
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Abstract

Background

Real-time quaking-induced conversion (RT-QuIC) of recombinant prion protein is a biomarker for Creutzfeldt-Jakob disease (CJD). RT-QuIC assesses a sample's seeding activity across multiple wells. We aim to model the test within a binomial framework and describe possible applications.Methods

This is a single-centre retrospective observational study. CJD and non-CJD cases with cerebrospinal fluid RT-QuIC were enrolled (2014-2018). The probability of a positive event in one well (θ+) for each group was assessed. θ+ can be used to calculate the posterior probability of disease (P_post) or as input parameters for computer simulations.Results

Data from 584 sporadic CJD (sCJD) and 226 non-CJD cases were used. Respectively, θ+ was 0.841 (95% CI 0.823 to 0.857) and 0.025 (95% CI 0.016 to 0.040). The distribution of RT-QuIC results did not differ between all sCJD samples and definite sCJD cases and across groups with different alleles at codon 129 of the PRNP gene. P_post was calculated for each result. The distribution of results did not differ significantly across years in def/prob-sCJD and non-CJD.Discussion

RT-QuIC results distribution and θ+ may be used for intra-laboratory quality control and P_post determination. Future studies should explore the utility of θ+ to increase diagnostic accuracy and inter-laboratory comparison.

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Cite

BibTeXRIS
BibTeX
@article{zavarella2026value,
  title = {{Value of positive RT-QuIC replicate number in sporadic Creutzfeldt-Jakob disease.}},
  author = {Matteo Zavarella and Peter Hermann and Susana da Silva Correia and Sezgi Canaslan Eyyuboglu and Matthias Schmitz and Massimo Filippi and Inga Zerr},
  journal = {BMJ neurology open},
  year = {2026},
  month = oct,
  doi = {10.1136/bmjno-2026-001863},
  url = {https://europepmc.org/article/MED/42968878},
  note = {CC BY-NC},
}
RIS
TY  - JOUR
TI  - Value of positive RT-QuIC replicate number in sporadic Creutzfeldt-Jakob disease.
AU  - Matteo Zavarella
AU  - Peter Hermann
AU  - Susana da Silva Correia
AU  - Sezgi Canaslan Eyyuboglu
AU  - Matthias Schmitz
AU  - Massimo Filippi
AU  - Inga Zerr
PY  - 2026
DA  - 2026/10/28
JO  - BMJ neurology open
DO  - 10.1136/bmjno-2026-001863
UR  - https://europepmc.org/article/MED/42968878
AB  - Background  Real-time quaking-induced conversion (RT-QuIC) of recombinant prion protein is a biomarker for Creutzfeldt-Jakob disease (CJD). RT-QuIC assesses a sample's seeding activity across multiple wells. We aim to model the test within a binomial framework and describe possible applications.Methods  This is a single-centre retrospective observational study. CJD and non-CJD cases with cerebrospinal fluid RT-QuIC were enrolled (2014-2018). The probability of a positive event in one well (θ+) for each group was assessed. θ+ can be used to calculate the posterior probability of disease (P_post) or as input parameters for computer simulations.Results  Data from 584 sporadic CJD (sCJD) and 226 non-CJD cases were used. Respectively, θ+ was 0.841 (95% CI 0.823 to 0.857) and 0.025 (95% CI 0.016 to 0.040). The distribution of RT-QuIC results did not differ between all sCJD samples and definite sCJD cases and across groups with different alleles at codon 129 of the PRNP gene. P_post was calculated for each result. The distribution of results did not differ significantly across years in def/prob-sCJD and non-CJD.Discussion  RT-QuIC results distribution and θ+ may be used for intra-laboratory quality control and P_post determination. Future studies should explore the utility of θ+ to increase diagnostic accuracy and inter-laboratory comparison.
SN  - 2632-6140
ER  -