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Original research
Comparison between plasma and cerebrospinal fluid biomarkers for the early diagnosis and association with survival in prion disease
  1. Samir Abu-Rumeileh1,
  2. Simone Baiardi1,
  3. Anna Ladogana2,
  4. Corrado Zenesini3,
  5. Anna Bartoletti-Stella3,
  6. Anna Poleggi2,
  7. Angela Mammana3,
  8. Barbara Polischi3,
  9. Maurizio Pocchiari2,
  10. Sabina Capellari1,3,
  11. Piero Parchi3,4
  1. 1 Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Bologna, Italy
  2. 2 Dipartimento di Neuroscienze, Istituto Superiore di Sanità, Roma, Italy
  3. 3 IRCCS Istituto Delle Scienze Neurologiche di Bologna, Bologna, Italy
  4. 4 Dipartimento di Medicina Specialistica Diagnostica e Sperimentale, Università di Bologna, Bologna, Italy
  1. Correspondence to Professor Piero Parchi, Dipartimento di Medicina Specialistica Diagnostica e Sperimentale, Università di Bologna, Bologna 40138, Italy; piero.parchi{at}unibo.it

Abstract

Objective To compare the diagnostic accuracy and the prognostic value of blood and cerebrospinal fluid (CSF) tests across prion disease subtypes.

Methods We used a single-molecule immunoassay to measure tau and neurofilament light chain (NfL) protein levels in the plasma and assessed CSF total(t)-tau, NfL and protein 14-3-3 levels in patients with prion disease (n=336), non-prion rapidly progressive dementias (n=106) and non-neurodegenerative controls (n=37). We then evaluated each plasma and CSF marker for diagnosis and their association with survival, taking into account the disease subtype, which is a strong independent prognostic factor in prion disease.

Results Plasma tau and NfL concentrations were higher in patients with prion disease than in non-neurodegenerative controls and non-prion rapidly progressive dementias. Plasma tau showed higher diagnostic value than plasma NfL, but a lower accuracy than the CSF proteins t-tau and 14-3-3. In the whole prion cohort, both plasma (tau and NfL) and CSF (t-tau, 14-3-3 and NfL) markers were significantly associated with survival and showed similar prognostic values. However, the intrasubtype analysis revealed that only CSF t-tau in sporadic Creutzfeldt-Jakob disease (sCJD) MM(V)1, plasma tau and CSF t-tau in sCJD VV2, and plasma NfL in slowly progressive prion diseases were significantly associated with survival after accounting for covariates.

Conclusions Plasma markers have lower diagnostic accuracy than CSF biomarkers. Plasma tau and NfL and CSF t-tau are significantly associated with survival in prion disease in a subtype-specific manner and can be used to improve clinical trial stratification and clinical care.

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Footnotes

  • Contributors SA-R, SB and PP designed the study. AB-S, AP, AM and BP performed biomarker experiments and genetic analyses. PP and SB performed neuropathological examinations. SA-R, SB, CZ and PP analysed data and interpreted the results. AL and MP provided samples and clinical data. SA-R, SB and PP wrote the manuscript draft. All authors critically revised the manuscript and approved its content before submission.

  • Funding This study was funded by grants from the Italian Ministry of Health (“Ricerca corrente”).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval The study was conducted according to the revised Declaration of Helsinki and Good Clinical Practice guidelines and approved by the ethics committee 'Area Vasta Emilia Centro' (approval number AVEC:18025, 113/2018/OSS/AUSLBO) and Istituto Superiore di Sanità (CE-ISS 09/266; 29 May 2009).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as online supplementary information. Data are available on reasonable request to the corresponding author.

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