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Blood phospho-tau in Alzheimer disease: analysis, interpretation, and clinical utility
Nature Reviews Neurology ( IF 28.2 ) Pub Date : 2022-05-18 , DOI: 10.1038/s41582-022-00665-2
Thomas K Karikari 1, 2 , Nicholas J Ashton 1, 3, 4, 5 , Gunnar Brinkmalm 1 , Wagner S Brum 1, 6 , Andréa L Benedet 1, 7 , Laia Montoliu-Gaya 1 , Juan Lantero-Rodriguez 1 , Tharick Ali Pascoal 2, 7 , Marc Suárez-Calvet 8, 9, 10, 11 , Pedro Rosa-Neto 7, 12, 13 , Kaj Blennow 1, 14 , Henrik Zetterberg 1, 14, 15, 16, 17
Affiliation  

Well-authenticated biomarkers can provide critical insights into the biological basis of Alzheimer disease (AD) to enable timely and accurate diagnosis, estimate future burden and support therapeutic trials. Current cerebrospinal fluid and molecular neuroimaging biomarkers fulfil these criteria but lack the scalability and simplicity necessary for widespread application. Blood biomarkers of adequate effectiveness have the potential to act as first-line diagnostic and prognostic tools, and offer the possibility of extensive population screening and use that is not limited to specialized centres. Accelerated progress in our understanding of the biochemistry of brain-derived tau protein and advances in ultrasensitive technologies have enabled the development of AD-specific phosphorylated tau (p-tau) biomarkers in blood. In this Review we discuss how new information on the molecular processing of brain p-tau and secretion of specific fragments into biofluids is informing blood biomarker development, enabling the evaluation of preanalytical factors that affect quantification, and informing harmonized protocols for blood handling. We also review the performance of blood p-tau biomarkers in the context of AD and discuss their potential contexts of use for clinical and research purposes. Finally, we highlight outstanding ethical, clinical and analytical challenges, and outline the steps that need to be taken to standardize inter-laboratory and inter-assay measurements.



中文翻译:

阿尔茨海默病中的血磷酸化 tau:分析、解释和临床应用

经过充分验证的生物标志物可以为阿尔茨海默病 (AD) 的生物学基础提供重要见解,从而实现及时准确的诊断、估计未来负担并支持治疗试验。目前的脑脊液和分子神经影像生物标志物满足这些标准,但缺乏广泛应用所需的可扩展性和简单性。足够有效的血液生物标志物有可能作为一线诊断和预后工具,并提供广泛的人群筛查和使用的可能性,而不仅限于专业中心。我们对脑源性 tau 蛋白的生物化学理解的加速进展和超灵敏技术的进步使得开发血液中 AD 特异性磷酸化 tau (p-tau) 生物标志物成为可能。在这篇综述中,我们讨论了关于脑 p-tau 分子加工和特定片段分泌到生物体液中的新信息如何为血液生物标志物的开发提供信息,从而能够评估影响量化的分析前因素,并为血液处理的协调方案提供信息。我们还回顾了血液 p-tau 生物标志物在 AD 中的表现,并讨论了它们用于临床和研究目的的潜在背景。最后,我们强调了突出的伦理、临床和分析挑战,并概述了标准化实验室间和测定间测量需要采取的步骤。能够评估影响量化的分析前因素,并为血液处理提供统一的协议。我们还回顾了血液 p-tau 生物标志物在 AD 中的表现,并讨论了它们用于临床和研究目的的潜在背景。最后,我们强调了突出的伦理、临床和分析挑战,并概述了标准化实验室间和测定间测量需要采取的步骤。能够评估影响量化的分析前因素,并为血液处理提供统一的协议。我们还回顾了血液 p-tau 生物标志物在 AD 中的表现,并讨论了它们用于临床和研究目的的潜在背景。最后,我们强调了突出的伦理、临床和分析挑战,并概述了标准化实验室间和测定间测量需要采取的步骤。

更新日期:2022-05-18
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