From the CSIRO Health and Biosecurity/Australian E-Health Research Centre (J.D.D.), Royal Brisbane and Women's Hospital, Herston, Queensland, Australia; R&D Department (V.P.-G., N.F., P.P., M.S.), Araclon Biotech Ltd, Zaragoza, Spain; and The Florey Institute of Neuroscience and Mental Health (C.F., V.L.V., C.L.M.), University of Melbourne, Parkville, Victoria, Australia.
Neurology. 2020 Apr 14;94(15):e1580-e1591. doi: 10.1212/WNL.0000000000009240. Epub 2020 Mar 16.
To explore whether the plasma total β-amyloid (Aβ) Aβ/Aβ 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.
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 Aβ/Aβ ratio in plasma (TP42/40) with regard to neocortical Aβ burden via PET standardized uptake value ratio (SUVR) and investigated both association with Aβ-PET status and correlation (and agreement) with SUVR.
The TP42/40 plasma ratio was significantly reduced in amyloid-PET-positive participants at all time points ( < 0.0001). Adjusting for covariates age, gender, ε4 allele status, and clinical classification clearly affects the significance, with values reduced and only comparisons at 54 months retaining significance ( = 0.006). Correlations with SUVR were similar across each time point, with Spearman ρ reaching -0.64 ( < 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.
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.
This study provides Class II evidence that plasma total Aβ/Aβ ratio is associated with neocortical amyloid burden as measured by PET SUVR.
通过探索澳大利亚成像、生物标志物和生活方式（AIBL）老龄化队列研究中的亚组中这两个变量之间的关系，探讨血浆总β-淀粉样蛋白（Aβ）Aβ/Aβ 比值是否是淀粉样蛋白-PET 状态的可靠预测因子。
在 3 个不同时间点（第 18 个月（n = 176）、第 36 个月（n = 169）和第 54 个月（n = 135））采集血浆样本，我们评估了血浆中总 Aβ/Aβ 比值（TP42/40）与通过 PET 标准化摄取比值（SUVR）测量的新皮层 Aβ 负荷，并研究了与 Aβ-PET 状态的关联以及与 SUVR 的相关性（和一致性）。
在所有时间点，淀粉样蛋白-PET 阳性参与者的 TP42/40 血浆比值均显著降低（<0.0001）。调整协变量（年龄、性别、ε4 等位基因状态和临床分类）后，这一结果仍然具有显著意义，与 SUVR 的相关性在各个时间点相似，Spearman ρ 值达到-0.64（<0.0001）。曲线下面积在各时间点均具有高度可重复性，36 个月时的 AUC 值为 0.880，54 个月时为 0.913。仅在健康对照组的评估中也发现了同样的关系。
本研究表明，该血浆测定法在 3 个时间点上可重复用于区分淀粉样蛋白-PET 阳性和阴性，这有助于大大降低针对临床前或前驱期疾病的临床试验的筛查失败率。
本研究提供了 II 级证据，表明血浆总 Aβ/Aβ 比值与 PET SUVR 测量的新皮层淀粉样蛋白负荷相关。
