Clinical value of novel blood‐based tau biomarkers in Creutzfeldt–Jakob disease

Abstract

BACKGROUNDThe diagnostic and prognostic performance of the novel fluid biomarkers brain‐derived tau (BD‐tau) and phospho‐tau217 (p‐tau217) in Creutzfeldt–Jakob disease (CJD) is not defined.METHODSWe measured cerebrospinal fluid (CSF) and plasma BD‐tau, p‐tau217, p‐tau181, total tau (t‐tau), neurofilament light (NfL), and 14‐3‐3 in 100 CJD patients, 100 with non‐prion rapidly progressive dementia (np‐RPD), 92 with mild cognitive impairment due to Alzheimer's disease (AD‐MCI), and 55 healthy controls (HC).RESULTSPlasma BD‐tau performed comparably to plasma t‐tau but had lower performance than CSF t‐tau (p < 0.001) and 14‐3‐3 (p = 0.014) in CJD versus np‐RPD differential diagnosis. Plasma BD‐tau diagnostic accuracy increased when ratioed to plasma p‐tau217, matching CSF 14‐3‐3. Plasma BD‐tau levels were associated with survival (p < 0.001), outperforming t‐tau and NfL.DISCUSSIONPlasma BD‐tau is a valuable marker for CJD prognostication. In the clinical setting, the plasma BD‐tau/p‐tau217 ratio provides an accurate, fast marker supporting the clinical diagnosis of CJD.Highlights The increase of plasma BD‐tau levels parallels that of CSF t‐tau in CJD. CSF p‐tau217 levels are significantly increased in CJD, reflecting a prion‐specific secondary tauopathy. Plasma p‐tau217 shows a distinct profile than CSF p‐tau217 in CJD. Plasma BD‐tau/p‐tau217 ratio is as accurate as CSF 14‐3‐3 in distinguishing CJD from np‐RPDs, including AD. BD‐tau represents a valuable blood‐based biomarker for CJD prognostication.