Liu Yibiao, Liu Xingyun, Liu Qiong, Xu Tailin
Longgang Clinical Institute of Shantou University Medical College, Longgang Central Hospital of Shenzhen, Shenzhen, Guangdong, 518116, China.
Institute for Advanced Study (IAS), College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, Guangdong, 518060, China.
Anal Chim Acta. 2025 Feb 22;1340:343654. doi: 10.1016/j.aca.2025.343654. Epub 2025 Jan 10.
Alzheimer's disease (AD) is a neurodegenerative disorder with a very long duration, posing a serious threat to people's life and health. To date, no medicine that can cure or reverse the disease has been developed or reported, so early diagnosis and timely intervention are essential. The concentration of Phosphorylated tau181 (P-tau181) in blood has been approved by FDA as a standard for assisting clinical diagnosis of AD.
In this study, a fluorescence biosensor based on vertical graphene-modified nano-gold film (VG@nAu) was developed for the grading of AD diagnosis by detecting P-tau181 protein in the blood. The VG@nAu substrate that produces hundreds of times IR800 molecular compared with a glass substrate, which is prepared by sputtering nano-gold onto vertical graphene surface. The detection limit of this fluorescence biosensor for P-tau181 is 0.82 pg/mL. The sensor also shows excellent selectivity and stability. Moreover, we analyzed the levels of P-tau181 in 16 clinical samples divided into four groups (HC group, SCD group, MCI group, and AD group) and found significant differences in P-tau181 levels. The grouping result based on the detection results using this biosensor is consistent with the grouping results of the clinical doctors.
This study achieves ultrasensitive detection of P-tau181 protein by constructing a fluorescent biosensor, which validates the feasibility of the VG@nAu-based fluorescence biosensor for the grading of AD diagnosis. This research provides a promising tool for ultrasensitive detecting biomarkers in clinical samples, indicating significant potential for its use in related diagnosing disease.
阿尔茨海默病（AD）是一种病程很长的神经退行性疾病，对人们的生命和健康构成严重威胁。迄今为止，尚未开发或报道出能够治愈或逆转该疾病的药物，因此早期诊断和及时干预至关重要。血液中磷酸化tau181（P-tau181）的浓度已被美国食品药品监督管理局（FDA）批准作为辅助AD临床诊断的标准。
在本研究中，通过检测血液中的P-tau181蛋白，开发了一种基于垂直石墨烯修饰纳米金膜（VG@nAu）的荧光生物传感器用于AD诊断分级。通过在垂直石墨烯表面溅射纳米金制备的VG@nAu基底产生的IR800分子比玻璃基底多数百倍。该荧光生物传感器对P-tau181的检测限为0.82 pg/mL。该传感器还表现出优异的选择性和稳定性。此外，我们分析了16个临床样本（分为四组：健康对照（HC）组、轻度认知障碍（SCD）组、轻度认知功能损害（MCI）组和AD组）中P-tau181的水平，发现P-tau181水平存在显著差异。基于该生物传感器检测结果的分组结果与临床医生的分组结果一致。
本研究通过构建荧光生物传感器实现了对P-tau181蛋白的超灵敏检测，验证了基于VG@nAu的荧光生物传感器用于AD诊断分级的可行性。本研究为临床样本中超灵敏检测生物标志物提供了一种有前景的工具，表明其在相关疾病诊断中的应用具有巨大潜力。
