Clinical utility of an antibody-free LC-MS method to detect brain amyloid deposition in cognitively unimpaired individuals from the screening visit of the A4 Study.
Clinical utility of an antibody-free LC-MS method to detect brain amyloid deposition in cognitively unimpaired individuals from the screening visit of the A4 Study.
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DOI：
10.1002/dad2.12451
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发表时间：
2023-04
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本研究探讨了血浆淀粉样β蛋白(Aβ)42/Aβ40在认知正常(CU)个体中识别脑淀粉样蛋白沉积的能力。在无症状阿尔茨海默病(A4)的抗淀粉样蛋白治疗(A4)研究中，采用Araclon Biotech的无抗体高效液相色谱-串联质谱仪(ABTEST-MS)对731例CU患者的血浆Aβ进行了定量，以评估Aβ42/Aβ40与Aβ正电子发射断层扫描的相关性。包括Aβ42/Aβ40、年龄、载脂蛋白Eε4和招募部位的模型识别Aβ状态，曲线下面积为0.88，总体准确率为81%。基于血浆的预筛查步骤可以节省高达Aβ正电子发射计算机断层扫描总数的42%。ABtest-MS准确识别了CU患者群体中的大脑淀粉样蛋白沉积，支持其在AD二级预防试验中的实施，以减少招募时间和成本。虽然一定程度的异质性是大型和多中心试验所固有的，但与其他免疫沉淀质谱学方法相比，ABtest-MS对分析前偏差的影响可能更强。血浆淀粉样β蛋白(Aβ)42/Aβ40准确地识别了无症状阿尔茨海默病(A4)抗淀粉样蛋白治疗研究中认知未受损个体的大脑Aβ沉积。将招聘地点纳入预测模型具有不可忽视的影响。基于血浆生物标记物的模型可以降低阿尔茨海默病二级预防试验的招募成本。与其他平台相比，无抗体液相色谱质谱方法可能对分析前的可变性更具稳健性。
This study explored the ability of plasma amyloid beta (Aβ)42/Aβ40 to identify brain amyloid deposition in cognitively unimpaired (CU) individuals. Plasma Aβ was quantified with an antibody‐free high‐performance liquid chromatography tandem mass spectrometry method from Araclon Biotech (ABtest‐MS) in a subset of 731 CU individuals from the screening visit of the Anti‐Amyloid Treatment in Asymptomatic Alzheimer's (A4) Study, to assess associations of Aβ42/Aβ40 with Aβ positron emission tomography (PET). A model including Aβ42/Aβ40, age, apolipoprotein E ε4, and recruitment site identified Aβ PET status with an area under the curve of 0.88 and an overall accuracy of 81%. A plasma‐based pre‐screening step could save up to 42% of the total number of Aβ PET scans. ABtest‐MS accurately identified brain amyloid deposition in a population of CU individuals, supporting its implementation in AD secondary prevention trials to reduce recruitment time and costs. Although a certain degree of heterogeneity is inherent to large and multicentric trials, ABtest‐MS could be more robust to pre‐analytical bias compared to other immunoprecipitation mass spectrometry methods. Plasma amyloid beta (Aβ)42/Aβ40 accurately identified brain Aβ deposition in cognitively unimpaired individuals from the Anti‐Amyloid Treatment in Asymptomatic Alzheimer's (A4) Study. The inclusion of the recruitment site in the predictive models has a non‐negligible effect. A plasma biomarker‐based model could reduce recruitment costs in Alzheimer's disease secondary prevention trials. Antibody‐free liquid chromatography mass spectrometry methods may be more robust to pre‐analytical variability than other platforms.