Research Center and Memory Clinic, Fundació ACE, Institut Català de Neurociències Aplicades, Universitat Internacional de Catalunya-Barcelona, C/ Marquès de Sentmenat, 57, 08029, Barcelona, Spain.
Araclon Biotech©, Zaragoza, Spain.
Alzheimers Res Ther. 2018 Nov 29;10(1):119. doi: 10.1186/s13195-018-0444-1.
Peripheral biomarkers that identify individuals at risk of developing Alzheimer's disease (AD) or predicting high amyloid beta (Aβ) brain burden would be highly valuable. To facilitate clinical trials of disease-modifying therapies, plasma concentrations of Aβ species are good candidates for peripheral AD biomarkers, but studies to date have generated conflicting results.
The Fundació ACE Healthy Brain Initiative (FACEHBI) study uses a convenience sample of 200 individuals diagnosed with subjective cognitive decline (SCD) at the Fundació ACE (Barcelona, Spain) who underwent amyloid florbetaben(F) (FBB) positron emission tomography (PET) brain imaging. Baseline plasma samples from FACEHBI subjects (aged 65.9 ± 7.2 years) were analyzed using the ABtest (Araclon Biotech). This test directly determines the free plasma (FP) and total plasma (TP) levels of Aβ40 and Aβ42 peptides. The association between Aβ40 and Aβ42 plasma levels and FBB-PET global standardized uptake value ratio (SUVR) was determined using correlations and linear regression-based methods. The effect of the APOE genotype on plasma Aβ levels and FBB-PET was also assessed. Finally, various models including different combinations of demographics, genetics, and Aβ plasma levels were constructed using logistic regression and area under the receiver operating characteristic curve (AUROC) analyses to evaluate their ability for discriminating which subjects presented brain amyloidosis.
FBB-PET global SUVR correlated weakly but significantly with Aβ42/40 plasma ratios. For TP42/40, this observation persisted after controlling for age and APOE ε4 allele carrier status (R = 0.193, p = 1.01E-09). The ROC curve demonstrated that plasma Aβ measurements are not superior to APOE and age in combination in predicting brain amyloidosis. It is noteworthy that using a simple preselection tool (the TP42/40 ratio with an empirical cut-off value of 0.08) optimizes the sensitivity and reduces the number of individuals subjected to Aβ FBB-PET scanners to 52.8%. No significant dependency was observed between APOE genotype and plasma Aβ measurements (p value for interaction = 0.105).
Brain and plasma Aβ levels are partially correlated in individuals diagnosed with SCD. Aβ plasma measurements, particularly the TP42/40 ratio, could generate a new recruitment strategy independent of the APOE genotype that would improve identification of SCD subjects with brain amyloidosis and reduce the rate of screening failures in preclinical AD studies. Independent replication of these findings is warranted.
识别有发生阿尔茨海默病（AD）风险或预测大脑中β淀粉样蛋白（Aβ）高负荷的外周生物标志物将具有重要价值。为了促进疾病修饰疗法的临床试验，Aβ 种的血浆浓度是外周 AD 生物标志物的良好候选物，但迄今为止的研究结果相互矛盾。
Fundació ACE 健康大脑倡议（FACEHBI）研究使用了 200 名在西班牙巴塞罗那的 Fundació ACE 诊断为主观认知下降（SCD）的个体的便利样本，这些个体接受了淀粉样蛋白 florbetaben（FBB）正电子发射断层扫描（PET）脑成像。使用 ABtest（Araclon Biotech）分析了 FACEHBI 受试者（年龄 65.9±7.2 岁）的基线血浆样本。该测试直接确定 Aβ40 和 Aβ42 肽的游离血浆（FP）和总血浆（TP）水平。使用相关性和基于线性回归的方法确定 Aβ40 和 Aβ42 血浆水平与 FBB-PET 全球标准化摄取值比（SUVR）之间的关联。还评估了 APOE 基因型对血浆 Aβ 水平和 FBB-PET 的影响。最后，使用逻辑回归和接收者操作特征曲线（AUROC）分析构建了包含不同组合的人口统计学、遗传学和 Aβ 血浆水平的各种模型，以评估它们区分有脑淀粉样蛋白的受试者的能力。
FBB-PET 全球 SUVR 与 Aβ42/40 血浆比值弱但显著相关。对于 TP42/40，在控制年龄和 APOE ε4 等位基因携带状态后，这一观察结果仍然存在（R=0.193，p=1.01E-09）。ROC 曲线表明，血浆 Aβ 测量在预测脑淀粉样蛋白方面并不优于 APOE 和年龄的组合。值得注意的是，使用简单的预筛选工具（经验截断值为 0.08 的 TP42/40 比值）可将需要进行 Aβ FBB-PET 扫描仪检查的个体数量优化至 52.8%。未观察到 APOE 基因型与血浆 Aβ 测量之间存在显著依赖性（交互作用 p 值=0.105）。
在诊断为 SCD 的个体中，大脑和血浆中的 Aβ 水平部分相关。Aβ 血浆测量，特别是 TP42/40 比值，可以生成一种新的招募策略，该策略独立于 APOE 基因型，可提高对有脑淀粉样蛋白的 SCD 患者的识别，并降低在临床前 AD 研究中筛选失败的发生率。需要对这些发现进行独立验证。
