新型血液中tau生物标志物在克雅氏病中的临床价值
Clinical value of novel blood-based tau biomarkers in Creutzfeldt-Jakob disease.
作者信息
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
机构信息
Department of Biomedical and Neuromotor Sciences (DiBiNeM), University of Bologna, Bologna, Italy.
Institute of Neuroscience and Physiology, University of Gothenburg, Mölndal, Sweden.
出版信息
Alzheimers Dement. 2025 Feb;21(2):e14422. doi: 10.1002/alz.14422. Epub 2024 Dec 6.
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.
背景
新型体液生物标志物脑源性tau蛋白（BD-tau）和磷酸化tau217（p-tau217）在克雅氏病（CJD）中的诊断和预后价值尚未明确。
方法
我们检测了100例CJD患者、100例非朊病毒快速进展性痴呆（np-RPD）患者、92例阿尔茨海默病所致轻度认知障碍（AD-MCI）患者和55例健康对照（HC）的脑脊液（CSF）及血浆中的BD-tau、p-tau217、p-tau181、总tau蛋白（t-tau）、神经丝轻链（NfL）和14-3-3。
结果
在CJD与np-RPD的鉴别诊断中，血浆BD-tau的表现与血浆t-tau相当，但低于脑脊液t-tau（p < 0.001）和14-3-3（p = 0.014）。当与血浆p-tau217进行比值计算时，血浆BD-tau的诊断准确性提高，与脑脊液14-3-3相当。血浆BD-tau水平与生存率相关（p < 0.001），优于t-tau和NfL。
讨论
血浆BD-tau是CJD预后评估的有价值标志物。在临床环境中，血浆BD-tau/p-tau217比值提供了一个准确、快速的标志物，支持CJD的临床诊断。
要点
CJD患者血浆BD-tau水平的升高与脑脊液t-tau水平的升高平行。CJD患者脑脊液p-tau217水平显著升高，反映了一种朊病毒特异性继发性tau蛋白病。CJD患者血浆p-tau217与脑脊液p-tau217表现出不同的特征。血浆BD-tau/p-tau217比值在区分CJD与np-RPD（包括AD）方面与脑脊液14-3-3一样准确。BD-tau是一种用于CJD预后评估的有价值的血液生物标志物。
Zotero 插件