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Journal of Neurology

, Volume 266, Issue 12, pp 3136–3143 | Cite as

Diagnostic value of surrogate CSF biomarkers for Creutzfeldt–Jakob disease in the era of RT-QuIC

  • Samir Abu-Rumeileh
  • Simone Baiardi
  • Barbara Polischi
  • Angela Mammana
  • Alessia Franceschini
  • Alison Green
  • Sabina Capellari
  • Piero ParchiEmail author
Original Communication

Abstract

Prion real-time quaking-induced conversion (RT-QuIC) is emerging as the most potent assay for the in vivo diagnosis of Creutzfeldt–Jakob disease (CJD), but its full application, especially as a screening test, is limited by suboptimal substrate availability, reagent costs, and incomplete assay standardization. Therefore, the search for the most informative cerebrospinal fluid (CSF) surrogate biomarker is still of primary importance. We compared the diagnostic accuracy of CSF protein 14-3-3, measured with both western blot (WB) and enzyme-linked immunosorbent assay (ELISA), total (t)-tau and neurofilament light chain protein (NfL) alone or in combination with RT-QuIC in 212 subjects with rapidly progressive dementia in which we reached a highly probable clinical diagnosis at follow-up or a definite neuropathological diagnosis. T-tau performed best as surrogate CSF biomarker for the diagnosis of CJD (91.3% sensitivity and 78.9% specificity). The 14-3-3 ELISA assay demonstrated a slightly higher diagnostic value compared to the WB analysis (76.9% vs. 72.2%), but both methods performed worse than the t-tau assay. NfL was the most sensitive biomarker for all sCJD subtypes (> 95%), including those with low values of t-tau or 14-3-3, but showed the lowest specificity (43.1%). When ELISA-based biomarkers were adopted as screening tests followed by RT-QuIC, t-tau correctly excluded a higher number of non-CJD cases compared to NfL and 14-3-3 ELISA. Our study showed that among the CSF surrogate biomarkers of potential application for the clinical diagnosis of CJD, t-tau performs best either alone or as screening test followed by RT-QuIC as a second-level confirmatory test.

Keywords

Prion disease Dementia Total tau 14-3-3 Neurofilament light chain 

Notes

Acknowledgements

We sincerely thank Dr. Byron Caughey for providing the substrate for IQ-CSF RT-QuIC. This work was supported by the Italian Ministry of Health (“Ricerca Corrente”).

Author contributions

Conceptualization: SA-R and PP; methodology, formal analysis and investigation: all authors; writing—original draft preparation: SA-R and PP; writing—review and editing: PP based on the critical revision of all authors—supervision: PP.

Compliance with ethical standards

Conflicts of interest

The authors declare that they have no conflict of interest.

Ethical standards

The study was conducted according to the revised Declaration of Helsinki and Good Clinical Practice guidelines and approved by the “Area Vasta Emilia Centro” ethics committee (CE-AVEC: 18025, 113/2018/OSS/AUSLBO). Informed consent was given by study participants or the next of kin.

Supplementary material

415_2019_9537_MOESM1_ESM.pdf (3.2 mb)
Supplementary file1 (PDF 3317 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Biomedical and Neuromotor SciencesUniversity of BolognaBolognaItaly
  2. 2.IRCCS Istituto delle Scienze Neurologiche di BolognaBolognaItaly
  3. 3.The National CJD Research and Surveillance UnitUniversity of EdinburghEdinburghUK
  4. 4.Department of Experimental Diagnostic and Specialty MedicineUniversity of BolognaBolognaItaly

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