Biomarkers in translational research of Alzheimer's disease.
Biomarkers in translational research of Alzheimer's disease.
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DOI：
10.1016/j.neuropharm.2010.04.006
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发表时间：
2010-09
影响因子：
4.7
通讯作者：
Holtzman, David M.
中科院分区：
文献类型：
--
作者：
Tarawneh, Rawan;Holtzman, David M.
淀粉样蛋白-β(A-β)和tau作为阿尔茨海默病(AD)的主要病理底物的鉴定和表征推动了人们寻找适合AD的生物标志物的努力。在过去的十年中，这一领域的研究主要集中在更好地了解蛋白质沉积的原理，将聚集与毒性和神经元死亡联系起来的机制，以及更好地了解脑组织、间质液体和脑脊液中的蛋白质动力学。虽然Aβ和tau是疾病的两个关键的病理介质，但这种多方面疾病的其他方面(如氧化应激、钙介导的毒性和神经炎症)正在被揭示，希望开发一种更全面的方法来探索疾病的机制。这不仅扩大了疾病修正疗法的可能领域，而且还允许引入新的、可能有用的液体和放射标志物来研究AD病理的存在和发展。毫无疑问，能够可靠地检测AD早期阶段的几种液体和成像生物标志物的识别将对临床试验的设计、同质研究人群的选择和疾病结果的评估具有重要意义。具有良好诊断特异性的标志物将有助于研究人员将临床前和可能患有AD的个体与没有AD病理或其他痴呆障碍的个体区分开来。随着疾病进展而变化的标记物可能会在评估疾病进展速度和潜在治疗药物对AD病理的疗效方面提供有用的帮助。对于这两个目的，脑脊液Aβ42、淀粉样蛋白成像和脑脊液tau似乎是非常好的AD病理存在的标志物，以及预测谁将从轻度脑梗塞进展到AD。体积磁共振成像还能很好地将MCI和AD患者与对照组区分开来，并能预测谁会从MCI发展为AD。也许生物标志物将具有最重要的作用，也是目前最需要的，在于识别认知正常但有AD病理证据的个体(即临床前AD)。这些人似乎可以用脑脊液Aβ42、淀粉样蛋白成像和脑脊液tau来识别。这些人最有可能从未来的疾病修改/预防疗法中受益，因为他们可以获得这些疗法，因此代表了该领域能够产生最大治疗影响的人群。
The identification and characterization of amyloid-β (Aβ) and tau as the main pathological substrates of Alzheimer’s disease (AD) has driven many efforts in search for suitable biomarkers for AD. In the last decade, research in this area has focused on developing a better understanding of the principles that govern protein deposition, mechanisms that link aggregation to toxicity and neuronal death, and a better understanding of protein dynamics in brain tissue, interstitial fluid and CSF. While Aβ and tau represent the two key pathological mediators of disease, other aspects of this multifaceted disease (e.g. oxidative stress, calcium-mediated toxicity, and neuroinflammation) are being unraveled, with the hope to develop a more comprehensive approach in exploring disease mechanisms. This has not only expanded possible areas for disease-modifying therapies, but has also allowed the introduction of novel, and potentially useful, fluid and radiological markers for the presence and progression of AD pathology. There is no doubt that the identification of several fluid and imaging biomarkers that can reliably detect the early stages of AD will have great implications in the design of clinical trials, in the selection of homogenous research populations, and in the assessment of disease outcomes. Markers with good diagnostic specificity will aid researchers in differentiating individuals with preclinical and probable AD from individuals who do not have AD pathology or have other dementing disorders. Markers that change with disease progression may offer utility in assessing the rates of disease progression and the efficacy of potential therapeutic agents on AD pathology. For both of these purposes, CSF Aβ42, amyloid imaging, and CSF tau appear to be very good markers of the presence of AD pathology as well as predictive or who will progress from MCI to AD. Volumetric MRI is also good at separating individuals with MCI and AD from controls and is predictive of who will progress from MCI to AD. Perhaps the most important role biomarkers will have, and the most needed at this time, lies in the identification of individuals who are cognitively normal, and yet have evidence of AD pathology (i.e. preclinical AD). Such individuals, it appears, can be identified with CSF Aβ42, amyloid imaging, and CSF tau. Such individuals are the most likely to benefit from future disease modifying/prevention therapies as they become available, and therefore represent the population in which the field can make the biggest therapeutic impact.
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影响因子：
11
作者：
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通讯作者：
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17.7
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作者：
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作者：
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