Comparison between plasma and cerebrospinal fluid biomarkers for the early diagnosis and association with survival in prion disease

J Neurol Neurosurg Psychiatry. 2020 Nov;91(11):1181-1188. doi: 10.1136/jnnp-2020-323826. Epub 2020 Sep 14.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 14-3-3 Proteins / blood*
  • 14-3-3 Proteins / cerebrospinal fluid
  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Biomarkers / cerebrospinal fluid
  • Creutzfeldt-Jakob Syndrome / blood*
  • Creutzfeldt-Jakob Syndrome / cerebrospinal fluid*
  • Creutzfeldt-Jakob Syndrome / classification
  • Creutzfeldt-Jakob Syndrome / diagnosis
  • Dementia / blood
  • Dementia / cerebrospinal fluid
  • Dementia / diagnosis
  • Disease Progression
  • Early Diagnosis
  • Encephalopathy, Bovine Spongiform / blood*
  • Encephalopathy, Bovine Spongiform / cerebrospinal fluid*
  • Encephalopathy, Bovine Spongiform / classification
  • Encephalopathy, Bovine Spongiform / diagnosis
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neurofilament Proteins / blood*
  • Neurofilament Proteins / cerebrospinal fluid
  • Prion Diseases / blood
  • Prion Diseases / cerebrospinal fluid
  • Prion Diseases / classification
  • Prion Diseases / diagnosis
  • Prognosis
  • Proportional Hazards Models
  • Survival Rate
  • tau Proteins / blood*
  • tau Proteins / cerebrospinal fluid


  • 14-3-3 Proteins
  • Biomarkers
  • Neurofilament Proteins
  • neurofilament protein L
  • tau Proteins

Supplementary concepts

  • Acquired CJD