基于血液的阿尔茨海默病 ATN 生物标志物：一项荟萃分析。

Blood-Based ATN Biomarkers of Alzheimer's Disease: A Meta-Analysis.

机构信息

Department of Psychiatry, University of Oxford, Oxford, UK.

Department of Psychology, University of Münster, Münster, Germany.

出版信息

J Alzheimers Dis. 2021;79(1):177-195. doi: 10.3233/JAD-200900.

DOI:10.3233/JAD-200900

PMID:33252080

Abstract

BACKGROUND

The Amyloid Tau Neurodegeneration (ATN) framework was proposed to define the biological state underpinning Alzheimer's disease (AD). Blood-based biomarkers offer a scalable alternative to the costly and invasive currently available biomarkers.

OBJECTIVE

In this meta-analysis we sought to assess the diagnostic performance of plasma amyloid (Aβ40, Aβ42, Aβ42/40 ratio), tangle (p-tau181), and neurodegeneration (total tau [t-tau], neurofilament light [NfL]) biomarkers.

METHODS

Electronic databases were screened for studies reporting biomarker concentrations for AD and control cohorts. Biomarker performance was examined by random-effect meta-analyses based on the ratio between biomarker concentrations in patients and controls.

RESULTS

83 studies published between 1996 and 2020 were included in the analyses. Aβ42/40 ratio as well as Aβ42 discriminated AD patients from controls when using novel platforms such as immunomagnetic reduction (IMR). We found significant differences in ptau-181 concentration for studies based on single molecule array (Simoa), but not for studies based on IMR or ELISA. T-tau was significantly different between AD patients and control in IMR and Simoa but not in ELISA-based studies. In contrast, NfL differentiated between groups across platforms. Exosome studies showed strong separation between patients and controls for Aβ42, t-tau, and p-tau181.

CONCLUSION

Currently available assays for sampling plasma ATN biomarkers appear to differentiate between AD patients and controls. Novel assay methodologies have given the field a significant boost for testing these biomarkers, such as IMR for Aβ, Simoa for p-tau181. Enriching samples through extracellular vesicles shows promise but requires further validation.

摘要

背景

淀粉样蛋白-tau 神经退行性变（ATN）框架被提出用于定义阿尔茨海默病（AD）的生物学状态。基于血液的生物标志物为目前可用的昂贵且有创的生物标志物提供了一种可扩展的替代方法。

目的

在这项荟萃分析中，我们旨在评估血浆淀粉样蛋白（Aβ40、Aβ42、Aβ42/40 比值）、缠结（p-tau181）和神经退行性变（总 tau [t-tau]、神经丝轻链 [NfL]）生物标志物的诊断性能。

方法

电子数据库被筛选以获取报告 AD 和对照队列中生物标志物浓度的研究。基于患者和对照之间生物标志物浓度的比值，通过随机效应荟萃分析来检查生物标志物的性能。

结果

纳入了 1996 年至 2020 年期间发表的 83 项研究。当使用免疫磁还原（IMR）等新型平台时，Aβ42/40 比值以及 Aβ42 可以区分 AD 患者和对照者。我们发现基于单分子阵列（Simoa）的研究中 p-tau-181 浓度存在显著差异，但基于 IMR 或 ELISA 的研究中则没有。IMR 和 Simoa 中的 t-tau 在 AD 患者和对照者之间存在显著差异，但 ELISA 研究中则没有。相比之下，NfL 在不同平台之间可以区分两组。外泌体研究显示，Aβ42、t-tau 和 p-tau181 可以在患者和对照者之间进行很好的区分。