Harmonization and standardization of biofluid-based biomarker measurements for AT(N) classification in Alzheimer's disease.
Harmonization and standardization of biofluid-based biomarker measurements for AT(N) classification in Alzheimer's disease.
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DOI：
10.1002/dad2.12465
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发表时间：
2023-07
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目前在脑脊液和血液中测量流体生物标志物用于阿尔茨海默病的诊断，并且是药物开发和临床试验中患者随访的有希望的目标。这些生物标志物被归类在一个公正的研究框架中，淀粉样蛋白（Aβ）、tau和神经变性（AT[N]）生物标志物系统，以帮助患者早期诊断和分层。依靠质谱法的计量方法已被用于标准物质和标准测量程序的开发。尽管液体生物标志物作为临床工具具有优异的性能，但它们往往在实验室之间存在重要的差异。对目前纳入AT(N)分类系统的生物标志物进行了标准化工作，涉及国家计量研究所、临床医生、研究人员和体外诊断提供者的合作。本文概述了标准化的当前活动。这些参考方法和参考物质可用于免疫测定的重新校准和标准化临界值的建立，从而更好地对阿尔茨海默病患者进行分层。AT(N)生物标记系统可以根据生物标记谱对AD患者进行分层。流体生物标志物的测量通常存在重要的实验室间差异，妨碍了标准化临界值的建立。关于目前包含在AT(N)框架中的流体生物标志物的标准化倡议概述。
Fluid biomarkers are currently measured in cerebrospinal fluid and blood for Alzheimer's disease diagnosis and are promising targets for drug development and for patients’ follow‐up in clinical trials. These biomarkers have been grouped in an unbiased research framework, the amyloid (Aβ), tau, and neurodegeneration (AT[N]) biomarker system to aid patients’ early diagnosis and stratification. Metrological approaches relying on mass spectrometry have been used for the development of reference materials and reference measurement procedures. Despite their excellent performances as clinical tools, fluid biomarkers often present an important between‐laboratory variation. Standardization efforts were carried out on the biomarkers currently included in the AT(N) classification system, involving the collaboration of national metrology institutes, clinicians, researchers, and in vitro diagnostic providers. This article provides an overview of current activities towards standardization. These reference methods and reference materials may be used for recalibration of immunoassays and the establishment of standardized cutoff values allowing a better stratification of Alzheimer's disease patients. The AT(N) biomarker system allows stratifying AD patients on the basis of biomarker profiles. Fluid biomarker measurements often present an important between‐laboratory variation preventing the establishment of standardized cutoff values. Overview on the standardization initiatives involving the fluid biomarkers currently included in the AT(N) framework.