Yoav D. Piura, Daniel J. Figdore, Christian Lachner, Joshua Bornhorst, Alicia Algeciras-Schimnich, Neill R. Graff-Radford, Gregory S. Day
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引用次数: 0
Abstract
INTRODUCTION
Plasma biomarkers of Alzheimer's disease (AD) represent accessible alternatives to positron emission tomography (PET) and cerebrospinal fluid (CSF)-based biomarkers in well-characterized cohorts. It remains to be determined whether performance is maintained in outpatient clinics comprised of patients with multiple causes of cognitive impairment.
METHODS
Plasma phosphorylated tau217 (p-tau217) and amyloid beta (Aβ) 42/40 were measured in 509 patients evaluated in a tertiary-care memory clinic. Biomarker performance was compared across diagnoses, referencing established cutpoints for positive and negative biomarkers.
RESULTS
Plasma p-tau217 distinguished patients with diagnoses of symptomatic AD with 95% sensitivity and 82% specificity. Integration of Aβ42 measurements (p-tau217/Aβ42) incrementally improved specificity (86%). Plasma p-tau217 and p-tau217/Aβ42 concentrations closely associated with established CSF biomarkers of AD (area under the curve [AUC]: 0.94 and 0.96, respectively). Reduced kidney function associated with elevated plasma p-tau217 and p-tau217/Aβ42 concentrations in patients without AD (referencing CSF biomarkers).
DISCUSSION
Plasma p-tau217 and p-tau217/Aβ42 concentrations demonstrated robust diagnostic performance in a heterogeneous clinical cohort; interpretation requires consideration of kidney function.
在特征明确的队列中，阿尔茨海默病（AD）的血浆生物标志物是正电子发射断层扫描（PET）和基于脑脊液（CSF）的生物标志物的可获得替代品。在由多种原因导致认知障碍的患者组成的门诊诊所中，是否能保持良好的表现仍有待确定。方法在一家三级保健记忆诊所评估509例患者的血浆磷酸化tau217 （p-tau217）和β淀粉样蛋白（a β） 42/40。在诊断过程中比较生物标志物的表现，参考阳性和阴性生物标志物的既定临界值。结果血浆p-tau217诊断有症状性AD的敏感性为95%，特异性为82%。整合a - β42测量（p-tau217/ a - β42）逐渐提高特异性（86%）。血浆p-tau217和p-tau217/ a - β42浓度与已建立的脑脊液AD生物标志物密切相关（曲线下面积[AUC]分别为0.94和0.96）。无AD患者血浆p-tau217和p-tau217/ a - β42浓度升高与肾功能降低相关（参考CSF生物标志物）。血浆p-tau217和p-tau217/ a - β42浓度在异质临床队列中显示出强大的诊断性能；解释需要考虑肾功能。血浆磷酸化tau217 （p-tau217）可靠地识别阿尔茨海默病临床患者。双切入点策略对86%的患者产生了明确的结果。血浆β淀粉样蛋白（Aβ）整合；p-tau217/ a - β42)最低限度地提高了诊断性能。肾功能不全患者血浆p-tau217水平升高。
期刊介绍：
Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.
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