Rabe Christina, Bittner Tobias, Jethwa Alexander, Suridjan Ivonne, Manuilova Ekaterina, Friesenhahn Michel, Stomrud Erik, Zetterberg Henrik, Blennow Kaj, Hansson Oskar
Genentech, Inc., South San Francisco, California, USA.
F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Alzheimers Dement. 2023 Apr;19(4):1393-1402. doi: 10.1002/alz.12801. Epub 2022 Sep 23.
Further evidence is needed to support the use of plasma amyloid β (Aβ) biomarkers as Alzheimer's disease prescreening tools. This study evaluated the clinical performance and robustness of plasma Aβ /Aβ for amyloid positivity prescreening.
Data were collected from 333 BioFINDER and 121 Alzheimer's Disease Neuroimaging Initiative study participants. Risk and predictive values versus percentile of plasma Aβ /Aβ evaluated the actionability of plasma Aβ /Aβ , and simulations modeled the impact of potential uncertainties and biases. Amyloid PET was the brain amyloidosis reference standard.
Elecsys plasma Aβ /Aβ could potentially rule out amyloid pathology in populations with low-to-moderate amyloid positivity prevalence. However, simulations showed small measurement or pre-analytical errors in Aβ and/or Aβ cause misclassifications, impacting sensitivity or specificity. The minor fold change between amyloid PET positive and negative cases explains the biomarkers low robustness.
Implementing plasma Aβ /Aβ for routine clinical use may pose significant challenges, with misclassification risks.
Plasma Aβ /Aβ ruled out amyloid PET positivity in a setting of low amyloid-positive prevalence. Including (pre-) analytical errors or measurement biases caused misclassifications. Plasma Aβ /Aβ had a low inherent dynamic range, independent of analytical method. Other blood biomarkers may be easier to implement as robust prescreening tools.
需要更多证据来支持将血浆淀粉样蛋白β（Aβ）生物标志物用作阿尔茨海默病的预筛查工具。本研究评估了血浆Aβ/Aβ用于淀粉样蛋白阳性预筛查的临床性能和稳健性。
收集了来自333名生物标志物发现者（BioFINDER）研究参与者和121名阿尔茨海默病神经影像学倡议（Alzheimer's Disease Neuroimaging Initiative）研究参与者的数据。血浆Aβ/Aβ的风险和预测值与百分位数用于评估血浆Aβ/Aβ的可操作性，模拟模型则模拟了潜在不确定性和偏差的影响。淀粉样蛋白PET是脑淀粉样变性的参考标准。
罗氏电化学发光法（Elecsys）检测的血浆Aβ/Aβ有可能排除淀粉样蛋白阳性患病率低至中等的人群中的淀粉样蛋白病变。然而，模拟结果显示，Aβ和/或Aβ的微小测量或分析前误差会导致错误分类，影响敏感性或特异性。淀粉样蛋白PET阳性和阴性病例之间的微小倍数变化解释了该生物标志物的低稳健性。
将血浆Aβ/Aβ用于常规临床应用可能会带来重大挑战，存在错误分类的风险。
在淀粉样蛋白阳性患病率较低的情况下，血浆Aβ/Aβ排除了淀粉样蛋白PET阳性。纳入（分析前）误差或测量偏差会导致错误分类。血浆Aβ/Aβ具有较低的固有动态范围，与分析方法无关。其他血液生物标志物可能更容易作为稳健的预筛查工具来应用。
