Jiao Bin, Liu Hui, Guo Lina, Liao Xinxin, Zhou Yafang, Weng Ling, Xiao Xuewen, Zhou Lu, Wang Xin, Jiang Yaling, Yang Qijie, Zhu Yuan, Zhou Lin, Zhang Weiwei, Wang Junling, Yan Xinxiang, Tang Beisha, Shen Lu
Department of Neurology, Xiangya Hospital, Central South University, Changsha, China.
National Clinical Research Center for Geriatric Disorders, Central South University, Changsha, China.
Front Aging Neurosci. 2021 Oct 27;13:749649. doi: 10.3389/fnagi.2021.749649. eCollection 2021.
Alzheimer's disease (AD) is the most common type of dementia and has no effective treatment to date. It is essential to develop a minimally invasive blood-based biomarker as a tool for screening the general population, but the efficacy remains controversial. This cross-sectional study aimed to evaluate the ability of plasma biomarkers, including amyloid β (Aβ), total tau (t-tau), and neurofilament light chain (NfL), to detect probable AD in the South Chinese population. A total of 277 patients with a clinical diagnosis of probable AD and 153 healthy controls with normal cognitive function (CN) were enrolled in this study. The levels of plasma Aβ42, Aβ40, t-tau, and NfL were detected using ultra-sensitive immune-based assays (SIMOA). Lumbar puncture was conducted in 89 patients with AD to detect Aβ42, Aβ40, t-tau, and phosphorylated (p)-tau levels in the cerebrospinal fluid (CSF) and to evaluate the consistency between plasma and CSF biomarkers through correlation analysis. Finally, the diagnostic value of plasma biomarkers was further assessed by constructing a receiver operating characteristic (ROC) curve. After adjusting for age, sex, and the apolipoprotein E () alleles, compared to the CN group, the plasma t-tau, and NfL were significantly increased in the AD group ( < 0.01, Bonferroni correction). Correlation analysis showed that only the plasma t-tau level was positively correlated with the CSF t-tau levels ( = 0.319, = 0.003). The diagnostic model combining plasma t-tau and NfL levels, and age, sex, and alleles, showed the best performance for the identification of probable AD [area under the curve (AUC) = 0.89, sensitivity = 82.31%, specificity = 83.66%]. Blood biomarkers can effectively distinguish patients with probable AD from controls and may be a non-invasive and efficient method for AD pre-screening.
阿尔茨海默病（AD）是最常见的痴呆类型，迄今为止尚无有效治疗方法。开发一种微创血液生物标志物作为筛查普通人群的工具至关重要，但疗效仍存在争议。这项横断面研究旨在评估血浆生物标志物，包括淀粉样β蛋白（Aβ）、总tau蛋白（t-tau）和神经丝轻链（NfL），在华南人群中检测可能的AD的能力。本研究共纳入277例临床诊断为可能AD的患者和153例认知功能正常（CN）的健康对照。使用基于超敏免疫分析（SIMOA）检测血浆Aβ42、Aβ40、t-tau和NfL水平。对89例AD患者进行腰椎穿刺，检测脑脊液（CSF）中的Aβ42、Aβ40、t-tau和磷酸化（p）-tau水平，并通过相关性分析评估血浆和CSF生物标志物之间的一致性。最后，通过构建受试者操作特征（ROC）曲线进一步评估血浆生物标志物的诊断价值。在调整年龄、性别和载脂蛋白E（）等位基因后，与CN组相比，AD组血浆t-tau和NfL显著升高（<0.01，Bonferroni校正）。相关性分析表明，只有血浆t-tau水平与CSF t-tau水平呈正相关（=0.319，=0.003）。结合血浆t-tau和NfL水平以及年龄、性别和等位基因的诊断模型在识别可能的AD方面表现最佳[曲线下面积（AUC）=0.89，敏感性=82.31%，特异性=83.66%]。血液生物标志物可以有效地区分可能患有AD的患者和对照，可能是一种无创且高效的AD预筛查方法。
