Papassotiropoulos Andreas, Fountoulakis Michael, Dunckley Travis, Stephan Dietrich A, Reiman Eric M
Division of Psychiatry Research, University of Zurich, Zurich, Switzerland.
J Clin Psychiatry. 2006 Apr;67(4):652-70. doi: 10.4088/jcp.v67n0418.
To provide an updated overview of the methods used in genetic, transcriptomic, and proteomic studies in Alzheimer's disease and to demonstrate the importance of those methods for the improvement of the current diagnostic and therapeutic possibilities.
MEDLINE-based search of 233 peer-reviewed articles published between 1975 and 2006.
Alzheimer's disease is a genetically heterogeneous disorder. Rare mutations in the amyloid precursor protein, presenilin 1, and presenilin 2 genes have shown the importance of the amyloid metabolism for its development. In addition, converging evidence from population-based genetic studies, gene expression studies, and protein profile studies in the brain and in the cerebrospinal fluid suggest the existence of several pathogenetic pathways such as amyloid precursor protein processing, beta-amyloid degradation, tau phosphorylation, proteolysis, protein misfolding, neuroinflammation, oxidative stress, and lipid metabolism.
The development of high-throughput genotyping methods and of elaborated statistical analyses will contribute to the identification of genetic risk profiles related to the development and course of this devastating disease. The integration of knowledge derived from genetic, transcriptomic, and proteomic studies will greatly advance our understanding of the causes of Alzheimer's disease, improve our capability of establishing an early diagnosis, help define disease subgroups, and ultimately help to pave the road toward improved and tailored treatments.
提供阿尔茨海默病遗传、转录组和蛋白质组学研究中所用方法的最新综述，并证明这些方法对于改善当前诊断和治疗可能性的重要性。
基于MEDLINE检索1975年至2006年间发表的233篇同行评议文章。
阿尔茨海默病是一种遗传异质性疾病。淀粉样前体蛋白、早老素1和早老素2基因中的罕见突变已表明淀粉样代谢对其发展的重要性。此外，基于人群的遗传研究、基因表达研究以及大脑和脑脊液中的蛋白质谱研究得出的一致证据表明存在多种致病途径，如淀粉样前体蛋白加工、β-淀粉样蛋白降解、tau蛋白磷酸化、蛋白水解、蛋白质错误折叠、神经炎症、氧化应激和脂质代谢。
高通量基因分型方法和精细统计分析的发展将有助于识别与这种毁灭性疾病的发展和进程相关的遗传风险概况。整合来自遗传、转录组和蛋白质组学研究的知识将极大地推进我们对阿尔茨海默病病因的理解，提高我们早期诊断的能力，帮助定义疾病亚组，并最终有助于为改进和个性化治疗铺平道路。
