Diagnostic performance and prediction of clinical progression of plasma phospho-tau181 in the Alzheimer's Disease Neuroimaging Initiative
Diagnostic performance and prediction of clinical progression of plasma phospho-tau181 in the Alzheimer's Disease Neuroimaging Initiative
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血浆磷酸化tau181在阿尔茨海默病神经影像研究中的诊断作用及临床进展预测
DOI：
10.1038/s41380-020-00923-z
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发表时间：
2020-10-26
影响因子：
11
通讯作者：
Zetterberg, Henrik
中科院分区：
文献类型：
--
作者：
Karikari, Thomas K.;Benedet, Andrea L.;Zetterberg, Henrik
虽然脑脊液(CSF)和正电子发射断层扫描(PET)淀粉样β蛋白(Aβ)和tau病理的生物标志物对阿尔茨海默病(AD)的诊断是准确的，但它们在临床和试验环境中的广泛实施受到高成本和可获得性有限的限制。血浆磷酸化tau181(p-tau181)是一种很有前景的血液生物标志物，它是AD的特异性标志物，与脑Aβ和tau病理相关，并预测未来的认知能力下降。在这项研究中，我们报告了来自阿尔茨海默病神经成像倡议(ADNI)的1000名患者中p-tau181的表现，包括认知未受损(CU)、轻度认知障碍(MCI)和以AβPET为特征的AD痴呆患者。我们证实，血浆p-tau181在阿尔茨海默病的临床前阶段升高，并在MCI和AD痴呆中进一步增加。临床被归类为AD痴呆但AβPET扫描阴性的个体显示几乎没有增加，但如果在AβPET改变之前脑脊液Aβ已经改变，那么血浆p-tau181就会增加。尽管是一项多中心研究，血浆p-tau181对AD痴呆的诊断准确率很高(AUC=85.3%；95%CI，81.4-89.2%)，并能区分阿尔茨海默病连续的Aβ-和Aβ+个体(AUC=76.9%；95%CI，74.0-79.8%)。较高的血浆p-tau181基线浓度准确地预测了未来的痴呆，并与脑脊液p-tau181的基线预测结果相当。对血浆p-tau181的纵向测量显示了较低的个体内变异性，这在寻求对治疗目标的可测量反应的疾病修改试验中可能是潜在的好处。这项研究增加了越来越多的证据，证明血浆p-tau181作为非侵入性诊断和预后工具用于AD，无论临床分期，这将在临床实践中极大地受益，并在临床试验招募中节省大量成本。
Whilst cerebrospinal fluid (CSF) and positron emission tomography (PET) biomarkers for amyloid-beta (A beta) and tau pathologies are accurate for the diagnosis of Alzheimer's disease (AD), their broad implementation in clinical and trial settings are restricted by high cost and limited accessibility. Plasma phosphorylated-tau181 (p-tau181) is a promising blood-based biomarker that is specific for AD, correlates with cerebral A beta and tau pathology, and predicts future cognitive decline. In this study, we report the performance of p-tau181 in >1000 individuals from the Alzheimer's Disease Neuroimaging Initiative (ADNI), including cognitively unimpaired (CU), mild cognitive impairment (MCI) and AD dementia patients characterized by A beta PET. We confirmed that plasma p-tau181 is increased at the preclinical stage of Alzheimer and further increases in MCI and AD dementia. Individuals clinically classified as AD dementia but having negative A beta PET scans show little increase but plasma p-tau181 is increased if CSF A beta has already changed prior to A beta PET changes. Despite being a multicenter study, plasma p-tau181 demonstrated high diagnostic accuracy to identify AD dementia (AUC = 85.3%; 95% CI, 81.4-89.2%), as well as to distinguish between A beta- and A beta+ individuals along the Alzheimer's continuum (AUC = 76.9%; 95% CI, 74.0-79.8%). Higher baseline concentrations of plasma p-tau181 accurately predicted future dementia and performed comparably to the baseline prediction of CSF p-tau181. Longitudinal measurements of plasma p-tau181 revealed low intra-individual variability, which could be of potential benefit in disease-modifying trials seeking a measurable response to a therapeutic target. This study adds significant weight to the growing body of evidence in the use of plasma p-tau181 as a non-invasive diagnostic and prognostic tool for AD, regardless of clinical stage, which would be of great benefit in clinical practice and a large cost-saving in clinical trial recruitment.