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

Abstract

BACKGROUND The 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.<p>

<p>METHODS We 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).

<p>RESULTS Plasma 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.

<p>DISCUSSION Plasma 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.