Clinical validity of cerebrospinal fluid Aβ42, tau, and phospho-tau as biomarkers for Alzheimer's disease in the context of a structured 5-phase development framework
Clinical validity of cerebrospinal fluid Aβ42, tau, and phospho-tau as biomarkers for Alzheimer's disease in the context of a structured 5-phase development framework
复制标题
DOI：
10.1016/j.neurobiolaging.2016.02.034
复制
发表时间：
2017-04-01
影响因子：
4.2
通讯作者：
Hansson, Oskar
中科院分区：
文献类型：
--
作者：
Mattsson, Niklas;Lonneborg, Anders;Hansson, Oskar
阿尔茨海默病（AD）的新诊断标准纳入了生物标志物，但其在前驱期（轻度认知障碍[ MCI]）临床实践中的成熟度尚不清楚。在这里，我们评估了脑脊液（CSF）β-淀粉样蛋白42（A β 42），总tau蛋白和磷酸化tau蛋白的生物标志物开发的5阶段框架的光。对于CSF生物标志物的第1阶段（识别有用的导联）和第2阶段（评估AD痴呆与对照的准确性），有充分的证据可用。第3阶段（MCI中的效用）部分实现。在随访时间较长的队列中，CSF A β 42、总tau和磷酸化tau对AD所致MCI的诊断准确性较高。第四阶段（在真实的世界中的表现）正在进行中，第五阶段的研究（量化影响和成本）即将到来。我们的研究结果突出了优先追求和使CSF生物标志物在临床中的正确使用。优先事项是通过引入全自动检测系统来减少测量变异性;提高MCI阶段对非AD神经认知疾病的诊断特异性;并澄清CSF生物标志物与其他生物标志物模式在临床实践和临床试验设计中的作用。这些努力目前正在进行中。(C)2016 Elsevier Inc. All rights reserved.
Novel diagnostic criteria for Alzheimer's disease (AD) incorporate biomarkers, but their maturity for implementation in clinical practice at the prodromal stage (mild cognitive impairment [ MCI]) is unclear. Here, we evaluate cerebrospinal fluid (CSF) beta-amyloid42 (A beta 42), total tau, and phosphorylated tau in the light of a 5-phase framework for biomarker development. Ample evidence is available for phase 1 (identifying useful leads) and phase 2 (assessing the accuracy for AD dementia versus controls) for CSF biomarkers. Phase 3 (utility in MCI) is partially achieved. In cohorts with long follow-up time, CSF A beta 42, total tau, and phosphorylated tau have high diagnostic accuracy for MCI due to AD. Phase 4 (performance in real world) is ongoing, and phase 5 studies (quantify impact and costs) are to come. Our results highlight priorities to pursue and to enable the proper use of CSF biomarkers in the clinic. Priorities are to reduce measurement variability by introduction of fully automated assay systems; to increase diagnostic specificity toward non-AD neurocognitive diseases at the MCI stage; and to clarify the role of CSF biomarkers versus other biomarker modalities in clinical practice and in design of clinical trials. These efforts are currently ongoing. (C) 2016 Elsevier Inc. All rights reserved.