University of North Texas Health Science Center, Department of Family Medicine and Institute for Translational Research, Fort Worth, TX, USA.
Alzheimer's Therapeutic Research Institute (ATRI), Keck School of Medicine, University of Southern California, San Diego, CA, USA.
J Alzheimers Dis. 2021;79(2):671-681. doi: 10.3233/JAD-201167.
The need for diagnostic biomarkers of cognitive decline is particularly important among aging adults with Down syndrome (DS). Growing empirical support has identified the utility of plasma derived biomarkers among neurotypical adults with mild cognitive impairment (MCI) and Alzheimer's disease (AD); however, the application of such biomarkers has been limited among the DS population.
This study aimed to investigate the cross-sectional diagnostic performance of plasma neurofilament light chain (Nf-L) and total-tau, individually and in combination among a cohort of DS adults.
Plasma samples were analyzed from n = 305 (n = 225 cognitively stable (CS); n = 44 MCI-DS; n = 36 DS-AD) participants enrolled in the Alzheimer's Biomarker Consortium -Down Syndrome.
In distinguishing DS-AD participants from CS, Nf-L alone produced an AUC of 90%, total-tau alone reached 74%, and combined reached an AUC of 86%. When age and gender were included, AUC increased to 93%. Higher values of Nf-L, total-tau, and age were all shown to be associated with increased risk for DS-AD. When distinguishing MCI-DS participants from CS, Nf-L alone produced an AUC of 65%, while total-tau alone reached 56%. A combined model with Nf-L, total-tau, age, and gender produced an AUC of 87%. Both higher values in age and total-tau were found to increase risk for MCI-DS; Nf-L levels were not associated with increased risk for MCI-DS.
Advanced assay techniques make total-tau and particularly Nf-L useful biomarkers of both AD pathology and clinical status in DS and have the potential to serve as outcome measures in clinical trials for future disease-modifying drugs.
对于唐氏综合征（Down syndrome，DS）患者等老年人群，诊断认知能力下降的生物标志物尤为重要。越来越多的经验证据表明，在患有轻度认知障碍（mild cognitive impairment，MCI）和阿尔茨海默病（Alzheimer's disease，AD）的神经认知正常成年人中，血浆衍生生物标志物具有一定的效用；然而，此类生物标志物在 DS 人群中的应用受到了限制。
本研究旨在通过分析 DS 成年人队列的血浆神经丝轻链（neurofilament light chain，Nf-L）和总 tau 水平，分别和联合检测，探究其在横断面诊断中的表现。
分析了参加阿尔茨海默病生物标志物联盟-唐氏综合征（Alzheimer's Biomarker Consortium -Down Syndrome，ABCD）研究的 305 名参与者（认知稳定 [cognitively stable，CS] 者 225 名、MCI-DS 者 44 名、DS-AD 者 36 名）的血浆样本。
与 CS 参与者相比，Nf-L 可单独将 DS-AD 参与者区分开，曲线下面积（area under the curve，AUC）为 90%，总 tau 为 74%，联合检测为 86%。当加入年龄和性别因素后，AUC 增加至 93%。Nf-L、总 tau 值较高和年龄较大均与 DS-AD 风险增加相关。与 CS 参与者相比，Nf-L 可单独将 MCI-DS 参与者区分开，AUC 为 65%，总 tau 为 56%。联合 Nf-L、总 tau、年龄和性别因素的模型 AUC 为 87%。总 tau 水平较高和年龄较大与 MCI-DS 风险增加相关，Nf-L 水平与 MCI-DS 风险增加无关。
先进的检测技术使总 tau 蛋白、尤其是 Nf-L 成为 DS 中 AD 病理和临床状态的有用生物标志物，有可能成为未来疾病修饰药物临床试验的结局指标。
