Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024
Clinical value of novel blood-based tau biomarkers in Creutzfeldt-Jakob disease.
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Bentivenga Giuseppe Mario, Gonzalez-Ortiz Fernando, Baiardi Simone, Kirsebom Bjørn-Eivind, Mastrangelo Andrea, Mammana Angela, Capellari Sabina, Fladby Tormod, Zetterberg Henrik, Blennow Kaj, Parchi Piero
Аннотация
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.
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).
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.
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.
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.
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).
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.
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.
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.