Dementia Research Laboratory, Department of Clinical Research, Singapore General Hospital, Outram Road, Singapore.
J Neurosci Res. 2010 May 1;88(6):1157-69. doi: 10.1002/jnr.22290.
Alzheimer's disease (AD) is characterized by a complex neurodegenerative process affecting multiple genes and proteins in the neocortex, many of which have not been well-studied. In this study, we investigated genome-wide gene alterations in the temporal cortex of a well-characterized cohort of AD patients using a recently developed microarray platform, and compared some of the transcript changes with immunoblotting. Of the 5485 genes found to be significantly altered in AD, there were consistent patterns of changes which show that the AD transcriptome in neocortex is characterized by changes indicative of synaptic dysfunction, perturbed neurotransmission and activation of neuroinflammation. We also highlighted several genes of potential pathogenic significance which have not been well studied in AD. The current study aims to add to the growing body of knowledge relating to gene changes in AD and provide further insights into pathogenic mechanisms and potential targets of pharmacotherapy.
阿尔茨海默病（AD）的特征是一种复杂的神经退行性过程，影响新皮层中的多个基因和蛋白质，其中许多尚未得到很好的研究。在这项研究中，我们使用最近开发的微阵列平台研究了经过充分特征描述的 AD 患者的颞叶皮层的全基因组基因改变，并将一些转录物变化与免疫印迹进行了比较。在 AD 中发现的 5485 个显著改变的基因中，存在一致的变化模式，表明新皮层中的 AD 转录组的特征是突触功能障碍、神经传递紊乱和神经炎症激活的改变。我们还强调了一些在 AD 中尚未得到很好研究的具有潜在致病性意义的基因。目前的研究旨在增加与 AD 中基因变化相关的不断增长的知识库，并为发病机制和潜在药物治疗靶点提供更多的见解。
