Cerebrospinal fluid analysis in Alzheimer's disease: technical issues and future developments
Cerebrospinal fluid analysis in Alzheimer's disease: technical issues and future developments
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DOI：
10.1007/s00415-014-7366-z
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发表时间：
2014-06-01
影响因子：
6
通讯作者：
Hampel, Harald
中科院分区：
文献类型：
--
作者：
Lista, Simone;Zetterberg, Henrik;Hampel, Harald
阿尔茨海默病（AD）是发病率、死亡率和全球主要流行病的主要原因。尽管临床评估仍然是患者管理和临床试验的重点，但这种评估具有重要的局限性。在这种情况下，脑脊液（CSF）生物标志物是重要的工具，以更好地识别高风险个体，及时准确地诊断AD，特别是在前驱轻度认知障碍阶段的疾病，并有效地诊断和治疗AD患者。功能基因组学、蛋白质组学、代谢组学和生物信息学的最新进展有望彻底改变对几种脑病理学的推定CSF标志物的无偏见调查，这些标志物可能是关于AD进展的各个阶段的简明信息。此外，有效的药物靶标的识别和AD的最佳治疗策略的开发将越来越依赖于更好地理解和整合系统生物学范式，这将允许预测一系列事件和由此产生的反应的生物网络引发的引入新的治疗化合物。在这种情况下，AD中基于生物学的无偏系统诊断和预后模型将由相关的综合分子组和受疾病影响的细胞神经元网络的关键分支组成。这样的特征性和无偏倚的生物标志物将更准确和全面地反映个体患者从早期无症状和症状前到最终前驱和症状性临床阶段的病理生理学（以及他们的个体遗传疾病倾向），最终增加未来疾病改善和预防性治疗的成功机会。
Alzheimer's disease (AD) is a leading cause of morbidity, mortality, and a major epidemic worldwide. Although clinical assessment continues to remain the keystone for patient management and clinical trials, such evaluation has important limitations. In this context, cerebrospinal fluid (CSF) biomarkers are important tools to better identify high-risk individuals, to diagnose AD promptly and accurately, especially at the prodromal mild cognitive impairment stage of the disease, and to effectively prognosticate and treat AD patients. Recent advances in functional genomics, proteomics, metabolomics, and bioinformatics will hopefully revolutionize unbiased inquiries into several putative CSF markers of cerebral pathology that may be concisely informative with regard to the various stages of AD progression through years and decades. Moreover, the identification of efficient drug targets and development of optimal therapeutic strategies for AD will increasingly rely on a better understanding and integration of the systems biology paradigm, which will allow predicting the series of events and resulting responses of the biological network triggered by the introduction of new therapeutic compounds. In this scenario, unbiased systems biology-based diagnostic and prognostic models in AD will consist of relevant comprehensive panels of molecules and key branches of the disease-affected cellular neuronal network. Such characteristic and unbiased biomarkers will more accurately and comprehensively reflect pathophysiology from the early asymptomatic and presymptomatic to the final prodromal and symptomatic clinical stages in individual patients (and their individual genetic disease predisposition), ultimately increasing the chances of success of future disease modifying and preventive treatments.