神经退行性变
生物标志物
正电子发射断层摄影术
病态的
τ蛋白
疾病
β淀粉样蛋白
脑脊液
病理
医学
神经科学
Tau病理学
阿尔茨海默病
陶氏病
神经影像学
心理学
生物
生物化学
作者
Charlotte E. Teunissen,Rachel Kolster,Gallen Triana‐Baltzer,Shorena Janelidze,Henrik Zetterberg,Hartmuth C. Kolb
摘要
Abstract The revised biomarker framework for diagnosis and staging of Alzheimer's disease (AD) relies on amyloid beta (Aβ) and tau pathologies as core markers, and markers for adjacent pathophysiology, such as neurodegeneration and inflammation. Many of the core fluid biomarkers are phosphorylated tau (p‐tau) fragments, with p‐tau217 showing a prominent association with Aβ and tau. While positron emission tomography (PET) imaging is well established, plasma p‐tau assays are newer and likely to reduce the use of expensive, and less accessible cerebrospinal fluid and PET imaging tests, thereby promoting wider access to AD screening. There is a need for greater understanding of how the various plasma p‐tau species reflect different pathological processes of AD and how different immunoassays perform. This review surveys the available immunoassays and highlights their strengths and limitations in different contexts of use. Assays need to be standardized to maximize their impact on AD clinical research, and patient diagnosis and management. Highlights Different plasma phosphorylated tau (p‐tau) species reflect different pathological processes of Alzheimer's disease (AD), with p‐tau231 showing the greatest association with the earliest increases in brain amyloid beta (Aβ) accumulation, while p‐tau217 shows greater association with both brain Aβ and early tau pathology, and other p‐tau and tau fragment species show greater association with later stages of brain tau pathology. Plasma p‐tau217 has proven to be an excellent biomarker for AD pathology due to its close association with both brain Aβ and tau pathology, as well as its large dynamic range. Many different assays with varying performance exist for the same p‐tau species, with mass spectrometry assays performing uniformly well, and several immunoassays achieving comparable performance. “Round robin” head‐to‐head studies have been performed to compare different assays for several key plasma biomarkers, including p‐tau181 and p‐tau217, but additional head‐to‐head studies are needed, especially for new analytes and for measuring performance in diverse populations. Plasma immunoassays have the potential to increase accessibility of early diagnostic testing for a broad population, including diverse historically under‐represented and under‐served populations, due to the potential to be implemented globally, including in primary care settings; however, further research is needed to validate the optimal cutoffs for each assay for real‐world clinical usage. Eventually, clinical implementation of a two‐step workflow may allow standalone use of plasma testing in certain contexts, minimizing the need for confirmation with costly and less accessible cerebrospinal fluid/positron emission tomography testing.
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