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阿尔茨海默病生物标志物胶质纤维酸性蛋白检测的临床应用评估

The Evaluation of Clinical Applications for the Detection of the Alzheimer's Disease Biomarker GFAP.

作者信息

Ozcelikay-Akyildiz Goksu, Karadurmus Leyla, Cetinkaya Ahmet, Uludag İnci, Ozcan Burcu, Unal Mehmet Altay, Sezginturk Mustafa Kemal, Ozkan Sibel A

机构信息

Department of Analytical Chemistry, Faculty of Pharmacy, Ankara University, Ankara, Türkiye.

Department of Analytical Chemistry, Faculty of Pharmacy, Adıyaman University, Adıyaman, Türkiye.

出版信息

Crit Rev Anal Chem. 2024 Aug 23:1-12. doi: 10.1080/10408347.2024.2393874.

Abstract

One of the most prevalent neurodegenerative diseases is Alzheimer's disease (AD). The hallmarks of AD include the accumulation of amyloid plaques and neurofibrillary tangles, which cause related secondary diseases, progressive neurodegeneration, and ultimately death. The most prevalent cell type in the human central nervous system, astrocytes, are crucial for controlling neuronal function. Glial fibrillary acidic protein (GFAP) is released from tissue into the bloodstream due to astrocyte breakdown in neurological diseases. Increased levels of GFAP in the serum can function as blood markers and be an effective prognostic indicator to help diagnose neurological conditions early on, from stroke to neurodegenerative diseases. The human central nervous system (CNS) is greatly affected by diseases associated with blood GFAP levels. These include multiple sclerosis, intracerebral hemorrhage, glioblastoma multiforme, traumatic brain injuries, and neuromyelitis optica. GFAP demonstrates a strong diagnostic capacity for projecting outcomes following an injury. Furthermore, the increased ability to identify GFAP protein fragments helps facilitate treatment, as it allows continuous screening of CNS injuries and early identification of potential recurrences. GFAP has recently gained attention due to data showing that the plasma biomarker is effective in identifying AD pathology. AD accounts for 60-70% of the approximately 50 million people with dementia worldwide. It is critical to develop molecular markers for AD, whose number is expected to increase to about 3 times and affect humans by 2050, and to investigate possible targets to confirm their effectiveness in the early diagnosis of AD. In addition, most diagnostic methods currently used are image-based and do not detect early disease, i.e. before symptoms appear; thus, treatment options and outcomes are limited. Therefore, recently developed methods such as point-of-care (POC), on-site applications, and enzyme-linked immunosorbent assay-polymerase chain reaction (ELISA-PCR) that provide both faster and more accurate results are gaining importance. This systematic review summarizes published studies with different approaches such as immunosensor, lateral flow, POC, ELISA-PCR, and molecularly imprinted polymer using GFAP, a potential blood biomarker to detect neurological disorders. Here, we also provide an overview of current approaches, analysis methods, and different future detection strategies for GFAP, the most popular biosensing field.

摘要

阿尔茨海默病(AD)是最常见的神经退行性疾病之一。AD的特征包括淀粉样斑块和神经原纤维缠结的积累,这些会引发相关的继发性疾病、进行性神经退行性变,并最终导致死亡。人类中枢神经系统中最普遍的细胞类型——星形胶质细胞,对于控制神经元功能至关重要。在神经疾病中,由于星形胶质细胞的分解,胶质纤维酸性蛋白(GFAP)会从组织释放到血液中。血清中GFAP水平的升高可作为血液标志物,成为一种有效的预后指标,有助于早期诊断从中风到神经退行性疾病等各种神经疾病。人类中枢神经系统(CNS)会受到与血液GFAP水平相关疾病的极大影响。这些疾病包括多发性硬化症、脑出血、多形性胶质母细胞瘤、创伤性脑损伤和视神经脊髓炎。GFAP在预测损伤后的结果方面具有很强的诊断能力。此外,识别GFAP蛋白片段能力的提高有助于治疗,因为它可以持续筛查中枢神经系统损伤并早期识别潜在的复发情况。最近,由于有数据表明血浆生物标志物在识别AD病理方面有效,GFAP受到了关注。在全球约5000万痴呆患者中,AD占60%-70%。开发AD的分子标志物至关重要,预计到2050年AD患者数量将增加到约3倍并影响更多人,同时研究可能的靶点以确认其在AD早期诊断中的有效性也很关键。此外,目前使用的大多数诊断方法都是基于图像的,无法在症状出现之前即疾病早期进行检测;因此,治疗选择和结果都很有限。所以,最近开发的如即时检测(POC)、现场应用以及酶联免疫吸附测定-聚合酶链反应(ELISA-PCR)等方法,因其能提供更快且更准确的结果而变得越来越重要。本系统综述总结了已发表的研究,这些研究采用了不同方法,如免疫传感器、侧向流动、POC、ELISA-PCR以及使用GFAP(一种检测神经疾病的潜在血液生物标志物)的分子印迹聚合物。在此,我们还概述了当前针对GFAP的方法、分析方法以及不同的未来检测策略,GFAP是最热门的生物传感领域之一。

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