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神经退行性疾病的生物标志物。

Biomarkers for neurodegenerative diseases.

作者信息

Henley Susie M D, Bates Gillian P, Tabrizi Sarah J

机构信息

Dementia Research Centre, Institute of Neurology, University College London, London, UK.

出版信息

Curr Opin Neurol. 2005 Dec;18(6):698-705. doi: 10.1097/01.wco.0000186842.51129.cb.

Abstract

PURPOSE OF REVIEW

A major goal of current clinical research in neurodegenerative diseases is to improve early detection of disease and presymptomatic detection of neuronal dysfunction. We also need better tools to assess disease progression in this group of disorders. Currently, many potential disease-modifying therapies are being developed and evaluated at the preclinical stage, and will lead to clinical trials in the near future for which biomarkers are urgently needed. This review summarizes the field of biomarker research in the major neurodegenerative diseases.

RECENT FINDINGS

Many different approaches are being undertaken to identify biomarkers and include imaging, neurophysiological and cognitive testing in addition to newer technologies such as biochemical, proteomic, metabanomic and gene array profiling of tissue and biofluids from patients. Key recent findings in each of these areas are discussed.

SUMMARY

The ideal biomarker needs to be easy to quantify and measure, reproducible, not subject to wide variation in the general population and unaffected by co-morbid factors. For evaluation of therapies the biomarker needs to change linearly with disease progression and closely correlate with established clinico-pathological parameters of the disease. It is unlikely that any one biomarker will fulfil all these characteristics, and it is likely that more than one biomarker will be needed for early diagnosis and similarly for evaluation of disease progression for therapeutic trials. For example, the combination of more detailed clinical assessments encompassing specific cognitive and neurophysiological testing, in addition to imaging, biochemical and genomic profiling, is likely to be needed.

摘要

综述目的

神经退行性疾病当前临床研究的一个主要目标是改善疾病的早期检测以及神经元功能障碍的症状前检测。我们还需要更好的工具来评估这组疾病的进展情况。目前,许多潜在的疾病修饰疗法正在临床前阶段进行研发和评估,并且在不久的将来将开展临床试验,为此迫切需要生物标志物。本综述总结了主要神经退行性疾病中生物标志物研究领域的情况。

最新发现

正在采用许多不同方法来识别生物标志物,除了对患者组织和生物流体进行生化、蛋白质组学、代谢组学和基因阵列分析等新技术外,还包括成像、神经生理学和认知测试。本文讨论了这些领域中近期的关键发现。

总结

理想的生物标志物需要易于量化和测量、可重复、在普通人群中不会有很大差异且不受共病因素影响。对于疗法评估,生物标志物需要随疾病进展呈线性变化,并与该疾病已确立的临床病理参数密切相关。不太可能有任何一种生物标志物能满足所有这些特性,早期诊断以及同样用于治疗试验的疾病进展评估可能需要不止一种生物标志物。例如,除了成像、生化和基因组分析外,可能还需要结合更详细的临床评估,包括特定的认知和神经生理学测试。

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