From the Department of Neurology (Y.L., S.E.S., J.G.B., V.O., K.G.M., R.J.B.), Division of Biostatistics (Y.L.), Knight Alzheimer's Disease Research Center (S.E.S., R.J.B.), and Hope Center for Neurological Disorders (R.J.B.), Washington University School of Medicine, St. Louis, MO; Departments of Psychiatry, Radiology and Biomedical Imaging, Medicine, and Neurology (M.W.W.), Center for Imaging and Neurodegenerative Diseases, Northern California Institute for Research and Education, Department of Veterans Affairs Medical Center, University of California San Francisco; Department of Pathology and Laboratory Medicine (S.M.L., J.Q.T., M.K.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; The Florey Institute of Neuroscience and Mental Health (C.L.M., C.J.F.), University of Melbourne, Victoria; Edith Cowan University (R.N.M.), Joondalup, Australia; Department of Clinical Sciences, Clinical Memory Research Unit (S.J., O.H.), Lund University; and Memory Clinic (O.H.), Skåne University Hospital, Malmö, Sweden.
Neurology. 2022 Feb 15;98(7):e688-e699. doi: 10.1212/WNL.0000000000013211. Epub 2021 Dec 14.
To determine the diagnostic accuracy of a plasma Aβ42/Aβ40 assay in classifying amyloid PET status across global research studies using samples collected by multiple centers that utilize different blood collection and processing protocols.
Plasma samples (n = 465) were obtained from 3 large Alzheimer disease (AD) research cohorts in the United States (n = 182), Australia (n = 183), and Sweden (n = 100). Plasma Aβ42/Aβ40 was measured by a high precision immunoprecipitation mass spectrometry (IPMS) assay and compared to the reference standards of amyloid PET and CSF Aβ42/Aβ40.
In the combined cohort of 465 participants, plasma Aβ42/Aβ40 had good concordance with amyloid PET status (receiver operating characteristic area under the curve [AUC] 0.84, 95% confidence interval [CI] 0.80-0.87); concordance improved with the inclusion of ε4 carrier status (AUC 0.88, 95% CI 0.85-0.91). The AUC of plasma Aβ42/Aβ40 with CSF amyloid status was 0.85 (95% CI 0.78-0.91) and improved to 0.93 (95% CI 0.89-0.97) with ε4 status. These findings were consistent across the 3 cohorts, despite differences in protocols. The assay performed similarly in both cognitively unimpaired and impaired individuals.
Plasma Aβ42/Aβ40 is a robust measure for detecting amyloid plaques and can be utilized to aid in the diagnosis of AD, identify those at risk for future dementia due to AD, and improve the diversity of populations enrolled in AD research and clinical trials.
This study provides Class II evidence that plasma Aβ42/Aβ40, as measured by a high precision IPMS assay, accurately diagnoses brain amyloidosis in both cognitively unimpaired and impaired research participants.
本研究旨在使用来自美国（n=182）、澳大利亚（n=183）和瑞典（n=100）三个大型阿尔茨海默病（AD）研究队列的样本，评估使用不同采血和处理方案的多个中心采集的血浆 Aβ42/Aβ40 检测在分类淀粉样蛋白 PET 状态方面的诊断准确性。
共纳入 465 例参与者，采集其血浆样本，采用高精度免疫沉淀质谱（IPMS）检测方法测定血浆 Aβ42/Aβ40，并与淀粉样蛋白 PET 和 CSF Aβ42/Aβ40 的参考标准进行比较。
在纳入的 465 例参与者的联合队列中，血浆 Aβ42/Aβ40 与淀粉样蛋白 PET 状态具有良好的一致性（受试者工作特征曲线下面积 [AUC] 0.84，95%置信区间 [CI] 0.80-0.87）；纳入 ε4 携带者状态后一致性提高（AUC 0.88，95%CI 0.85-0.91）。血浆 Aβ42/Aβ40 与 CSF 淀粉样蛋白状态的 AUC 为 0.85（95%CI 0.78-0.91），纳入 ε4 状态后提高至 0.93（95%CI 0.89-0.97）。这些发现与 3 个队列一致，尽管方案存在差异。该检测方法在认知正常和认知受损个体中表现相似。
血浆 Aβ42/Aβ40 是检测淀粉样斑块的有力指标，可用于辅助 AD 的诊断，识别未来因 AD 导致痴呆的风险人群，并提高 AD 研究和临床试验中入组人群的多样性。
本研究提供了 II 级证据，表明采用高精度 IPMS 检测方法测定的血浆 Aβ42/Aβ40 可准确诊断认知正常和受损研究参与者的脑淀粉样变。
