Plasma Aβ42/40 ratio alone or combined with FDG-PET can accurately predict amyloid-PET positivity: a cross-sectional analysis from the AB255 Study
Plasma Aβ42/40 ratio alone or combined with FDG-PET can accurately predict amyloid-PET positivity: a cross-sectional analysis from the AB255 Study
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DOI：
10.1186/s13195-019-0549-1
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发表时间：
2019-12-01
影响因子：
9
通讯作者：
Antunez, Carmen
中科院分区：
文献类型：
--
作者：
Perez-Grijalba, Virginia;Arbizu, Javier;Antunez, Carmen
背景 为了促进阿尔茨海默病疾病缓解疗法的人群筛查和临床试验，支持性生物标志物信息是必要的。本研究旨在探讨血浆淀粉样蛋白-β (Aβ) 水平与淀粉样蛋白 PET 测量的大脑中 Aβ 病理性积累的关系。血浆 Aβ 42/40 比率单独或与基于 FDG-PET 的神经变性生物标志物组合都被评估为潜在的 AD 生物标志物。方法 我们纳入了 AB255 研究中接受 PiB-PET 扫描的 39 名认知正常受试者和 20 名轻度认知障碍患者。使用 ABtest 试剂盒对血浆中总 A β 40 和 A β 42 水平 (TP42/40) 进行定量。将受试者分为 A β-PET 阳性或阴性，并通过逻辑回归和受试者操作特征分析评估 TP42/40 检测 A β-PET 阳性的能力。血浆 Aβ 生物标志物和 FDG-PET 的组合被进一步评估为脑淀粉样变性检测和诊断分类的改进。结果 18 名受试者 (30.5%) A beta-PET 呈阳性。 TP42/40 比率单独确定 A beta-PET 状态，曲线下面积 (AUC) 为 0.881（95% 置信区间 [CI] = 0.779-0.982）。 TP42/40 检测 A beta-PET 阳性受试者的判别性能在 Youden 截止值处产生的敏感性和特异性值分别为 77.8% 和 87.5%，阳性预测值为 0.732，阴性预测值为 0.900。在调整显着协变量的模型后，所有这些参数均得到改善。应用 TP42/40 作为顺序诊断检查中的第一个筛查工具将使 A beta-PET 扫描的数量减少 64%。 FDG-PET 评分和血浆 A beta 生物标志物的组合被发现是最准确的 A beta-PET 预测因子，AUC 为 0.965（95% CI = 0.913-0.100）。结论 血浆 TP42/40 比率显示出作为筛查工具在阿尔茨海默病临床前和前驱阶段识别脑 Aβ 阳性的相关且显着的潜力。
Background To facilitate population screening and clinical trials of disease-modifying therapies for Alzheimer's disease, supportive biomarker information is necessary. This study was aimed to investigate the association of plasma amyloid-beta (A beta) levels with the presence of pathological accumulation of A beta in the brain measured by amyloid-PET. Both plasma A beta 42/40 ratio alone or combined with an FDG-PET-based biomarker of neurodegeneration were assessed as potential AD biomarkers. Methods We included 39 cognitively normal subjects and 20 patients with mild cognitive impairment from the AB255 Study who had undergone PiB-PET scans. Total A beta 40 and A beta 42 levels in plasma (TP42/40) were quantified using ABtest kits. Subjects were dichotomized as A beta-PET positive or negative, and the ability of TP42/40 to detect A beta-PET positivity was assessed by logistic regression and receiver operating characteristic analyses. Combination of plasma A beta biomarkers and FDG-PET was further assessed as an improvement for brain amyloidosis detection and diagnosis classification. Results Eighteen (30.5%) subjects were A beta-PET positive. TP42/40 ratio alone identified A beta-PET status with an area under the curve (AUC) of 0.881 (95% confidence interval [CI] = 0.779-0.982). Discriminating performance of TP42/40 to detect A beta-PET-positive subjects yielded sensitivity and specificity values at Youden's cutoff of 77.8% and 87.5%, respectively, with a positive predictive value of 0.732 and negative predictive value of 0.900. All these parameters improved after adjusting the model for significant covariates. Applying TP42/40 as the first screening tool in a sequential diagnostic work-up would reduce the number of A beta-PET scans by 64%. Combination of both FDG-PET scores and plasma A beta biomarkers was found to be the most accurate A beta-PET predictor, with an AUC of 0.965 (95% CI = 0.913-0.100). Conclusions Plasma TP42/40 ratio showed a relevant and significant potential as a screening tool to identify brain A beta positivity in preclinical and prodromal stages of Alzheimer's disease.