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阿尔茨海默病的生物标志物

Biomarkers for Alzheimer's Disease.

作者信息

Guzman-Martinez Leonardo, Maccioni Ricardo B, Farías Gonzalo A, Fuentes Patricio, Navarrete Leonardo P

机构信息

Laboratory of Neurosciences, International Center for Biomedicine (ICC), Chile.

Faculty of Sciences, University of Chile, Santiago, Chile.

出版信息

Curr Alzheimer Res. 2019;16(6):518-528. doi: 10.2174/1567205016666190517121140.

Abstract

Alzheimer´s disease (AD) and related forms of dementia are increasingly affecting the aging population throughout the world, at an alarming rate. The World Alzheimer´s Report indicates a prevalence of 46.8 million people affected by AD worldwide. As population ages, this number is projected to triple by 2050 unless effective interventions are developed and implemented. Urgent efforts are required for an early detection of this disease. The ultimate goal is the identification of viable targets for the development of molecular markers and validation of their use for early diagnosis of AD that may improve treatment and the disease outcome in patients. The diagnosis of AD has been difficult to resolve since approaches for early and accurate detection and follow-up of AD patients at the clinical level have been reported only recently. Some proposed AD biomarkers include the detection of pathophysiological processes in the brain in vivo with new imaging techniques and novel PET ligands, and the determination of pathogenic proteins in cerebrospinal fluid showing anomalous levels of hyperphosphorylated tau and low Aβ peptide. These biomarkers have been increasingly accepted by AD diagnostic criteria and are important tools for the design of clinical trials, but difficulties in accessibility to costly and invasive procedures have not been completely addressed in clinical settings. New biomarkers are currently being developed to allow determinations of multiple pathological processes including neuroinflammation, synaptic dysfunction, metabolic impairment, protein aggregation and neurodegeneration. Highly specific and sensitive blood biomarkers, using less-invasive procedures to detect AD, are derived from the discoveries of peripheric tau oligomers and amyloid variants in human plasma and platelets. We have also developed a blood tau biomarker that correlates with a cognitive decline and also with neuroimaging determinations of brain atrophy.

摘要

阿尔茨海默病(AD)及相关形式的痴呆症正以惊人的速度日益影响着全球老年人口。《世界阿尔茨海默病报告》指出,全球有4680万人受AD影响。随着人口老龄化,预计到2050年这一数字将增至三倍,除非开发并实施有效的干预措施。迫切需要做出努力以早期检测这种疾病。最终目标是确定可行的靶点,用于开发分子标记物并验证其在AD早期诊断中的应用,这可能改善患者的治疗和疾病结局。由于临床层面早期准确检测和随访AD患者的方法直到最近才被报道,AD的诊断一直难以解决。一些提议的AD生物标志物包括用新的成像技术和新型PET配体在体内检测大脑中的病理生理过程,以及测定脑脊液中显示异常高磷酸化tau水平和低Aβ肽水平的致病蛋白。这些生物标志物已越来越被AD诊断标准所接受,并且是设计临床试验的重要工具,但在临床环境中,昂贵且侵入性程序难以获得的问题尚未得到完全解决。目前正在开发新的生物标志物,以确定包括神经炎症、突触功能障碍、代谢损害、蛋白质聚集和神经退行性变在内的多种病理过程。使用侵入性较小的程序检测AD的高特异性和敏感性血液生物标志物,源自对人血浆和血小板中外周tau寡聚体和淀粉样蛋白变体的发现。我们还开发了一种血液tau生物标志物,它与认知能力下降以及脑萎缩的神经影像学测定相关。

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