背景:纵向早发性阿尔茨海默病研究(LEADS)的一个目标是定义早发性阿尔茨海默病(EOAD)的流体生物标志物特征。
方法:脑脊液(CSF)中Aβ1-40,Aβ1-42,总tau(tTau)的浓度,pTau181,VILIP-1,SNAP-25,神经颗粒素(Ng),神经丝轻链(NfL),通过免疫测定对165名LEADS参与者进行了YKL-40和YKL-40的测定。评估了生物标志物浓度与诊断组和标准认知测试的相关性。
结果:生物标志物彼此相关。CSFAβ42/40,pTau181,tTau,EOAD中的SNAP-25和Ng与认知正常和早发性非AD痴呆显著不同;NfL,YKL-40和VILIP-1没有。跨群体,除SNAP-25外,所有生物标志物均与认知相关.在EOAD组内,Aβ42/40,NfL,Ng,SNAP-25与至少一项认知测量相关。
结论:这项研究提供了对散发性EOAD中CSF生物标志物的全面分析,可以为EOAD临床试验设计提供信息。
One goal of the Longitudinal Early Onset Alzheimer\'s Disease Study (LEADS) is to define the fluid biomarker characteristics of early-onset Alzheimer\'s disease (EOAD).
Cerebrospinal fluid (CSF) concentrations of Aβ1-40, Aβ1-42, total tau (tTau), pTau181, VILIP-1, SNAP-25, neurogranin (Ng), neurofilament light chain (NfL), and YKL-40 were measured by immunoassay in 165 LEADS participants. The associations of biomarker concentrations with diagnostic group and standard cognitive tests were evaluated.
Biomarkers were correlated with one another. Levels of CSF Aβ42/40, pTau181, tTau, SNAP-25, and Ng in EOAD differed significantly from cognitively normal and early-onset non-AD dementia; NfL, YKL-40, and VILIP-1 did not. Across groups, all biomarkers except SNAP-25 were correlated with cognition. Within the EOAD group, Aβ42/40, NfL, Ng, and SNAP-25 were correlated with at least one cognitive measure.
This study provides a comprehensive analysis of CSF biomarkers in sporadic EOAD that can inform EOAD clinical trial design.