基于 ELISA 和 SIMOA 的血浆 Aβ 比值定量比较用于脑淀粉样血管病的早期检测。
Comparison of ELISA- and SIMOA-based quantification of plasma Aβ ratios for early detection of cerebral amyloidosis.
机构信息
Laboratory for Molecular Neurobiomarker Research, Department of Neurosciences, KU Leuven, box 7003, Herestraat 49, 3000, Leuven, Belgium.
Laboratory Medicine, UZ Leuven, Leuven, Belgium.
出版信息
Alzheimers Res Ther. 2020 Dec 5;12(1):162. doi: 10.1186/s13195-020-00728-w.
BACKGROUND
Blood-based amyloid biomarkers may provide a non-invasive, cost-effective and scalable manner for detecting cerebral amyloidosis in early disease stages.
METHODS
In this prospective cross-sectional study, we quantified plasma Aβ/Aβ ratios with both routinely available ELISAs and novel SIMOA Amyblood assays, and provided a head-to-head comparison of their performances to detect cerebral amyloidosis in a nondemented elderly cohort (n = 199). Participants were stratified according to amyloid-PET status, and the performance of plasma Aβ/Aβ to detect cerebral amyloidosis was assessed using receiver operating characteristic analysis. We additionally investigated the correlations of plasma Aβ ratios with amyloid-PET and CSF Alzheimer's disease biomarkers, as well as platform agreement using Passing-Bablok regression and Bland-Altman analysis for both Aβ isoforms.
RESULTS
ELISA and SIMOA plasma Aβ/Aβ detected cerebral amyloidosis with identical accuracy (ELISA: area under curve (AUC) 0.78, 95% CI 0.72-0.84; SIMOA: AUC 0.79, 95% CI 0.73-0.85), and both increased the performance of a basic demographic model including only age and APOE-ε4 genotype (p ≤ 0.02). ELISA and SIMOA had positive predictive values of respectively 41% and 36% in cognitively normal elderly and negative predictive values all exceeding 88%. Plasma Aβ/Aβ correlated similarly with amyloid-PET for both platforms (Spearman ρ = - 0.32, p < 0.0001), yet correlations with CSF Aβ/t-tau were stronger for ELISA (ρ = 0.41, p = 0.002) than for SIMOA (ρ = 0.29, p = 0.03). Plasma Aβ levels demonstrated poor agreement between ELISA and SIMOA with concentrations of both Aβ and Aβ measured by SIMOA consistently underestimating those measured by ELISA.
CONCLUSIONS
ELISA and SIMOA demonstrated equivalent performances in detecting cerebral amyloidosis through plasma Aβ/Aβ, both with high negative predictive values, making them equally suitable non-invasive prescreening tools for clinical trials by reducing the number of necessary PET scans for clinical trial recruitment.
TRIAL REGISTRATION
EudraCT 2009-014475-45 (registered on 23 Sept 2009) and EudraCT 2013-004671-12 (registered on 20 May 2014, https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-004671-12/BE ).
背景
基于血液的淀粉样蛋白生物标志物可能为在早期疾病阶段检测脑淀粉样血管病提供一种非侵入性、具有成本效益且可扩展的方法。
方法
在这项前瞻性的横断面研究中，我们使用常规的 ELISA 和新型的 SIMOA Amyblood 测定法来定量血浆 Aβ/Aβ 比值，并对其在无痴呆的老年队列（n=199）中检测脑淀粉样血管病的性能进行了直接比较。根据淀粉样蛋白-PET 状态对参与者进行分层，并使用接收者操作特征分析评估血浆 Aβ/Aβ 检测脑淀粉样血管病的性能。我们还研究了血浆 Aβ 比值与淀粉样蛋白-PET 和 CSF 阿尔茨海默病生物标志物的相关性，以及使用 Passing-Bablok 回归和 Bland-Altman 分析对于两种 Aβ 异构体的平台一致性。
结果
ELISA 和 SIMOA 血浆 Aβ/Aβ 检测脑淀粉样血管病的准确性相同（ELISA：曲线下面积（AUC）为 0.78，95%CI 为 0.72-0.84；SIMOA：AUC 为 0.79，95%CI 为 0.73-0.85），并且均提高了仅包含年龄和 APOE-ε4 基因型的基本人口统计学模型的性能（p≤0.02）。在认知正常的老年人中，ELISA 和 SIMOA 的阳性预测值分别为 41%和 36%，阴性预测值均超过 88%。ELISA 和 SIMOA 与两种平台的淀粉样蛋白-PET 相关性相似（Spearman ρ=-0.32，p<0.0001），但与 ELISA（ρ=0.41，p=0.002）相比，与 CSF Aβ/t-tau 的相关性更强与 SIMOA（ρ=0.29，p=0.03）。ELISA 和 SIMOA 之间的血浆 Aβ 水平一致性较差，SIMOA 测量的 Aβ 和 Aββ 浓度均一致低于 ELISA 测量的浓度。
结论
ELISA 和 SIMOA 通过血浆 Aβ/Aβ 在检测脑淀粉样血管病方面表现出相同的性能，均具有较高的阴性预测值，通过减少临床试验招募所需的 PET 扫描数量，它们均成为用于临床试验的非侵入性预筛选工具。
试验注册
EudraCT 2009-014475-45（于 2009 年 9 月 23 日注册）和 EudraCT 2013-004671-12（于 2014 年 5 月 20 日注册，https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-004671-12/BE）。
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