Total Aβ42/Aβ40 ratio in plasma predicts amyloid-PET status, independent of clinical AD diagnosis
Total Aβ42/Aβ40 ratio in plasma predicts amyloid-PET status, independent of clinical AD diagnosis
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DOI：
10.1212/wnl.0000000000009240
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发表时间：
2020-04-14
期刊：
影响因子：
9.9
通讯作者：
Sarasa, Manuel
中科院分区：
文献类型：
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作者：
Doecke, James D.;Perez-Grijalba, Virginia;Sarasa, Manuel
目的 通过在澳大利亚影像、生物标志物和生活方式 (AIBL) 老龄队列研究的一个子集中探讨血浆总 β-淀粉样蛋白 (Aβ) Aβ(42)/Aβ(40) 比率是否是淀粉样蛋白-PET 状态的可靠预测因子，这两个变量之间的关联。方法 在第 18 个月 (n = 176)、第 36 个月 (n = 169) 和第 54 个月 (n = 135) 3 个不同的时间点采集血浆样本，通过 PET 标准化摄取值比 (SUVR) 评估血浆中总 A β (42)/A β (40) 比率 (TP42/40) 与新皮质 A β 负荷的关系，并研究与 A β-PET 状态的关联以及与 A β-PET 状态的相关性（和一致性）。越野车。结果 淀粉样蛋白-PET 阳性参与者的 TP42/40 血浆比率在所有时间点均显着降低 (p < 0.0001)。调整协变量年龄、性别、APOE epsilon 4 等位基因状态和临床分类明显影响显着性，p 值降低，仅 54 个月时的比较保留显着性 (p = 0.006)。每个时间点与 SUVR 的相关性相似，Spearman rho 达到 -0.64 (p < 0.0001)。曲线下面积值在不同时间点上具有高度可重复性，值范围从 36 个月时的 0.880 到 54 个月时的 0.913。仅在对健康对照组的评估中，发现了相同的关系。结论 目前的研究表明，血浆检测在 3 个时间点上区分淀粉样蛋白 PET 阳性和阴性的重现性，这有助于大幅降低针对临床前或前驱疾病的临床试验的筛查失败率。证据分类 本研究提供了 II 类证据，表明血浆总 Aβ(42)/Aβ(40) 比率与 PET SUVR 测量的新皮质淀粉样蛋白负荷相关。
Objective To explore whether the plasma total beta-amyloid (A beta) A beta(42)/A beta(40) ratio is a reliable predictor of the amyloid-PET status by exploring the association between these 2 variables in a subset of the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging cohort. Methods Taking plasma samples at 3 separate time points, month 18 (n = 176), month 36 (n = 169), and month 54 (n = 135), we assessed the total A beta(42)/A beta(40) ratio in plasma (TP42/40) with regard to neocortical A beta burden via PET standardized uptake value ratio (SUVR) and investigated both association with A beta-PET status and correlation (and agreement) with SUVR. Results The TP42/40 plasma ratio was significantly reduced in amyloid-PET-positive participants at all time points (p < 0.0001). Adjusting for covariates age, gender, APOE epsilon 4 allele status, and clinical classification clearly affects the significance, with p values reduced and only comparisons at 54 months retaining significance (p = 0.006). Correlations with SUVR were similar across each time point, with Spearman rho reaching -0.64 (p < 0.0001). Area under the curve values were highly reproducible over time points, with values ranging from 0.880 at 36 months to 0.913 at 54 months. In assessments of the healthy control group only, the same relationships were found. Conclusions The current study demonstrates reproducibility of the plasma assay to discriminate between amyloid-PET positive and negative over 3 time points, which can help to substantially reducing the screening rate of failure for clinical trials targeting preclinical or prodromal disease. Classification of evidence This study provides Class II evidence that plasma total A beta(42)/A beta(40) ratio is associated with neocortical amyloid burden as measured by PET SUVR.