用于测量血浆中p217 + tau的高灵敏度检测方法的开发与验证。

Development and validation of a high-sensitivity assay for measuring p217+tau in plasma.

作者信息

Triana-Baltzer Gallen, Moughadam Setareh, Slemmon Randy, Van Kolen Kristof, Theunis Clara, Mercken Marc, Kolb Hartmuth C

机构信息

Neuroscience Biomarkers Janssen Research & Development La Jolla California USA.

Neuroscience Department Janssen Research & Development Beerse Belgium.

出版信息

Alzheimers Dement (Amst). 2021 May 27;13(1):e12204. doi: 10.1002/dad2.12204. eCollection 2021.

INTRODUCTION

Diagnosis of Alzheimer's disease (AD) based on amyloid beta (A), pathologic tau (T), and neurodegeneration (N) biomarkers in peripheral fluids promises to accelerate clinical trials and intercept disease earlier.

METHODS

Qualification of a Simoa plasma p217+tau assay was performed, followed by clinical utility evaluation in a cohort of 227 subjects with broad A and T spectrum.

RESULTS

The p217+tau plasma assay was accurate, precise, dilution linear, and highly sensitive. All measured samples were within linear range of the assay, presented higher concentration in AD versus healthy controls ( < .0001), and plasma and cerebrospinal fluid levels correlated (r = 0.35). The plasma p217+tau results were predictive of central T and A status (area under the curve = 0.90 and 0.90, respectively) with low false +/- rates.

DISCUSSION

The assay described here exhibits good technical performance and shows potential as a highly accurate peripheral biomarker for A or T status in AD and cognitively normal subjects.

引言

基于外周液中淀粉样β蛋白（A）、病理性tau蛋白（T）和神经退行性变（N）生物标志物诊断阿尔茨海默病（AD）有望加速临床试验并更早地干预疾病。

方法

对一种单分子阵列（Simoa）血浆p217 + tau检测方法进行了验证，随后在227名具有广泛A和T谱的受试者队列中进行了临床实用性评估。

结果

p217 + tau血浆检测方法准确、精确、具有稀释线性且高度灵敏。所有测量样本均在检测方法的线性范围内，与健康对照相比，AD患者样本浓度更高（<0.0001），血浆和脑脊液水平具有相关性（r = 0.35）。血浆p217 + tau检测结果能够预测中枢T和A状态（曲线下面积分别为0.90和0.90），假阳性/阴性率较低。