Proteomics Unit, IRCCS Centro S. Giovanni di Dio-Fatebenefratelli, Brescia, Italy. rghidoni @ fatebenefratelli.it
Neurodegener Dis. 2011;8(6):413-20. doi: 10.1159/000327756. Epub 2011 Jun 25.
Alzheimer's disease (AD) is the major cause of dementia in the elderly. The biochemical changes that precede AD may be present up to 20 years before the clinical manifestation of the disease. The translational development of AD biomarkers may be theoretically achieved via two different strategies: the first strategy can be defined as 'knowledge-based' (deductive method), while the second one is a hypothesis-generating 'unbiased' approach (inductive strategy). The 'knowledge-based' approach relies on a direct understanding of the neuropathological processes that underlie the development of AD. In contrast, the 'unbiased' approach involves the use of modern techniques including proteomics and bioinformatics that allow unbiased investigations of numerous putative markers that may be informative with regard to AD. Cerebrospinal fluid (CSF) dosage of neuropathological AD-associated proteins has already been incorporated into the neurochemical diagnosis of AD, attesting the relevance of translational research. In the last few years, biomarker discovery research has successfully utilized genomics and proteomics for the identification of several promising molecular markers for AD. In the present article, we discuss the present state of the art and the future challenges in the search of CSF biomarkers for AD.
阿尔茨海默病（AD）是老年人痴呆的主要原因。在疾病的临床表现出现之前，可能会出现 AD 之前的生化变化。AD 生物标志物的转化发展可能通过两种不同的策略来实现：第一种策略可以定义为“基于知识”（演绎方法），而第二种是生成假说的“无偏见”方法（归纳策略）。“基于知识”的方法依赖于对导致 AD 发展的神经病理学过程的直接理解。相比之下，“无偏见”的方法涉及使用现代技术，包括蛋白质组学和生物信息学，这些技术可以对许多可能与 AD 相关的假定标记物进行无偏见的调查。脑脊液（CSF）中神经病理 AD 相关蛋白的含量已经被纳入 AD 的神经化学诊断中，证明了转化研究的相关性。在过去的几年中，生物标志物发现研究成功地利用基因组学和蛋白质组学来鉴定 AD 的几个有前途的分子标记物。在本文中，我们讨论了 AD 的 CSF 生物标志物研究的现状和未来挑战。
