Department of Gerontology, Federal University of São Carlos (UFSCar), Rodovia Washington Luís, km 235, São Carlos, SP, 13565-905, Brazil.
Department of Nursing, Federal University of São Carlos (UFSCar), São Carlos, Brazil.
Alzheimers Res Ther. 2021 Jan 8;13(1):18. doi: 10.1186/s13195-020-00750-y.
Blood-based biomarkers for Alzheimer's disease (AD) are highly needed in clinic practice. So far, the gold standards for AD diagnosis are brain neuroimaging and beta-amyloid peptide, total tau, and phosphorylated tau in cerebrospinal fluid (CSF); however, they are not attractive for large-scale screening. Blood-based biomarkers allow an initial large-scale screening of patients under suspicion that could later be tested for the already established CSF biomarkers. To this regard, in this study, we evaluated whether plasma ADAM10 levels would be predictors of declines in cognition in community-dwelling older adults after a 3-year period follow-up.
This was a 3-year longitudinal cohort study that included 219 community-dwelling older adults. Sociodemographic, clinical, lifestyle, depressive symptoms (GDS), and cognitive data (Mini-Mental State Examination, MMSE; Clock Drawing test, CDT) were gathered. The measurement of ADAM10 plasma levels was performed using a sandwich ELISA kit. Bivariate comparisons between groups were performed using Wilcoxon-Mann-Whitney for continuous data and Pearson's chi-square tests with Yates continuity correction for categorical data. Longitudinal analyzes of changes in the MMSE scores were performed using linear mixed-effects modeling.
Baseline MMSE scores and ADAM10 levels were significantly associated with MMSE scores on the follow-up assessment. When analyzing the interaction with time, normal MMSE scores and the ADAM10 plasma levels at baseline presented a significant and independent negative association with MMSE score values on the follow-up assessment. The analyses also showed that the predictive effect of ADAM10 plasma levels on decreasing MMSE scores on follow-up seems to be more pronounced in participants with normal MMSE, when compared with those with altered MMSE scores at baseline.
Considering that ADAM10 increase in plasma is detected as soon as in mild cognitive impairment (MCI) patients, the results presented here may support the complementary clinical use of this biomarker, in addition to the classical AD biomarkers. Taken together, these results provide the first direct evidence that changes in ADAM10 plasma levels are predictors of cognitive worsening in older adults. Moreover, this work can shed light on the study of blood biomarkers for AD and contribute to the advancement of the area.
阿尔茨海默病（AD）的血液生物标志物在临床实践中非常需要。到目前为止，AD 诊断的金标准是脑神经影像学和脑脊液（CSF）中的β-淀粉样蛋白、总tau 和磷酸化 tau；然而，它们不适合大规模筛查。血液生物标志物允许对疑似患者进行初步的大规模筛查，然后可以对已经建立的 CSF 生物标志物进行测试。为此，在这项研究中，我们评估了在 3 年随访后，血浆 ADAM10 水平是否可预测社区居住的老年患者认知能力下降。
这是一项为期 3 年的纵向队列研究，纳入了 219 名社区居住的老年人。收集了社会人口统计学、临床、生活方式、抑郁症状（GDS）和认知数据（简易精神状态检查，MMSE；画钟测验，CDT）。使用夹心 ELISA 试剂盒测量 ADAM10 血浆水平。使用 Wilcoxon-Mann-Whitney 检验进行连续数据的组间比较，使用 Pearson 卡方检验和 Yates 连续性校正进行分类数据的组间比较。使用线性混合效应模型对 MMSE 评分的变化进行纵向分析。
基线 MMSE 评分和 ADAM10 水平与随访评估时的 MMSE 评分显著相关。当分析与时间的交互作用时，正常 MMSE 评分和基线时的 ADAM10 血浆水平与随访评估时的 MMSE 评分值呈显著负相关。分析还表明，与基线时 MMSE 评分异常的参与者相比，ADAM10 血浆水平对随访时 MMSE 评分下降的预测作用在正常 MMSE 评分的参与者中更为明显。
鉴于 ADAM10 在血浆中的增加早在轻度认知障碍（MCI）患者中就被检测到，本研究结果可能支持除经典 AD 生物标志物外，该生物标志物的补充临床应用。综上所述，这些结果提供了 ADAM10 血浆水平变化是老年患者认知恶化的预测因素的直接证据。此外，这项工作可以为 AD 血液生物标志物的研究提供启示，并为该领域的发展做出贡献。
