用于阿尔茨海默病诊断的 CSF 磷酸化 tau T181 和 T217 生物标志物的临床性能的头对头比较。

Head-to-head comparison of clinical performance of CSF phospho-tau T181 and T217 biomarkers for Alzheimer's disease diagnosis.

机构信息

Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Department of Neurology, University Medical Centre Ljubljana, Ljubljana, Slovenia.

出版信息

Alzheimers Dement. 2021 May;17(5):755-767. doi: 10.1002/alz.12236. Epub 2020 Nov 30.

INTRODUCTION

Phosphorylated tau (p-tau) in cerebrospinal fluid (CSF) is an established Alzheimer's disease (AD) biomarker. Novel immunoassays targeting N-terminal and mid-region p-tau181 and p-tau217 fragments are available, but head-to-head comparison in clinical settings is lacking.

METHODS

N-terminal-directed p-tau217 (N-p-tau217), N-terminal-directed p-tau181 (N-p-tau181), and standard mid-region p-tau181 (Mid-p-tau181) biomarkers in CSF were evaluated in three cohorts (n = 503) to assess diagnostic performance, concordance, and associations with amyloid beta (Aβ).

RESULTS

CSF N-p-tau217 and N-p-tau181 had better concordance (88.2%) than either with Mid-p-tau181 (79.7%-82.7%). N-p-tau217 and N-p-tau181 were significantly increased in early mild cognitive impairment (MCI)-AD (A+T-N-) without changes in Mid-p-tau181 until AD-dementia. N-p-tau217 and N-p-tau181 identified Aβ pathophysiology (area under the curve [AUC] = 94.8%-97.1%) and distinguished MCI-AD from non-AD MCI (AUC = 82.6%-90.5%) signficantly better than Mid-p-tau181 (AUC = 91.2% and 70.6%, respectively). P-tau biomarkers equally differentiated AD from non-AD dementia (AUC = 99.1%-99.8%).

DISCUSSION

N-p-tau217 and N-p-tau181 could improve diagnostic accuracy in prodromal-AD and clinical trial recruitment as both identify Aβ pathophysiology and differentiate early MCI-AD better than Mid-p-tau181.

简介

脑脊液（CSF）中磷酸化 tau（p-tau）是一种已确立的阿尔茨海默病（AD）生物标志物。新型针对 N 端和中间区 p-tau181 和 p-tau217 片段的免疫测定法已经可用，但在临床环境中缺乏头对头比较。

方法

在三个队列（n=503）中评估了 N 端定向的 p-tau217（N-p-tau217）、N 端定向的 p-tau181（N-p-tau181）和标准中间区 p-tau181（Mid-p-tau181）生物标志物，以评估诊断性能、一致性以及与淀粉样蛋白β（Aβ）的相关性。

结果

CSF N-p-tau217 和 N-p-tau181 的一致性（88.2%）优于 Mid-p-tau181（79.7%-82.7%）。在早期轻度认知障碍（MCI）-AD（A+T-N-）中，N-p-tau217 和 N-p-tau181 显著增加，而 Mid-p-tau181 直到 AD 痴呆才发生变化。N-p-tau217 和 N-p-tau181 可识别 Aβ 病理生理学（曲线下面积 [AUC] = 94.8%-97.1%），并将 MCI-AD 与非 AD MCI 区分开来（AUC = 82.6%-90.5%）明显优于 Mid-p-tau181（AUC = 91.2%和 70.6%）。p-tau 生物标志物在区分 AD 与非 AD 痴呆方面同样有效（AUC = 99.1%-99.8%）。