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Comparison between plasma and cerebrospinal fluid biomarkers for the early diagnosis and association with survival in prion disease
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Comparison between plasma and cerebrospinal fluid biomarkers for the early diagnosis and association with survival in prion disease
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Journal Article
Comparison between plasma and cerebrospinal fluid biomarkers for the early diagnosis and association with survival in prion disease
2020
Overview
ObjectiveTo compare the diagnostic accuracy and the prognostic value of blood and cerebrospinal fluid (CSF) tests across prion disease subtypes.MethodsWe 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.ResultsPlasma 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.ConclusionsPlasma 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.
Publisher
BMJ Publishing Group Ltd,BMJ Publishing Group LTD
Subject
/ 14-3-3 Proteins - cerebrospinal fluid
/ Age
/ Aged
/ Biomarkers - cerebrospinal fluid
/ Creutzfeldt-Jakob Syndrome - blood
/ Creutzfeldt-Jakob Syndrome - cerebrospinal fluid
/ Creutzfeldt-Jakob Syndrome - classification
/ Creutzfeldt-Jakob Syndrome - diagnosis
/ Dementia - cerebrospinal fluid
/ Encephalopathy, Bovine Spongiform - blood
/ Encephalopathy, Bovine Spongiform - cerebrospinal fluid
/ Encephalopathy, Bovine Spongiform - classification
/ Encephalopathy, Bovine Spongiform - diagnosis
/ Female
/ Humans
/ Male
/ Neurofilament Proteins - blood
/ Neurofilament Proteins - cerebrospinal fluid
/ Ostomy
/ Plasma
/ Prion Diseases - cerebrospinal fluid
/ Prion Diseases - classification
/ Proteins
/ Software
