McKusick Nathans Institute of Genetic Medicine, Johns Hopkins University, School of Medicine, 733 N. Broadway, Baltimore, MD, USA.
Neurobiol Aging. 2011 Dec;32(12):2319.e27-34. doi: 10.1016/j.neurobiolaging.2010.04.019. Epub 2010 Jun 8.
Alzheimer's disease (AD) is a common cause of dementia with a strong genetic component and risk sharply increasing with age. We performed two parallel microarray experiments to independently identify genes involved in normal aging and genes involved in AD using RNA extracted from the temporal lobe of 22 late onset AD and 23 control brain donors. We found that AD is accompanied by significant changes in the expression of many genes with upregulation of genes involved in inflammation and in transcription regulation and downregulation of genes involved in neuronal functions. The changes with healthy aging involved multiple genes but were not as strong. Replicating and strengthening previous reports, we find a highly significant overlap between genes changing expression with age and those changing in AD, and we observe that those changes are most often in the same direction. This result supports an overlap between the biological processes of normal aging and susceptibility to AD and suggests that age related genes expression changes might increase the risk of developing AD.
阿尔茨海默病(AD)是痴呆的常见病因,具有很强的遗传成分,且风险随年龄的增长急剧增加。我们进行了两项平行的微阵列实验,使用从 22 名晚发性 AD 和 23 名对照脑供体的颞叶提取的 RNA,分别独立鉴定参与正常衰老和 AD 的基因。我们发现 AD 伴随着许多基因表达的显著变化,涉及炎症和转录调节的基因上调,涉及神经元功能的基因下调。与健康衰老相关的变化涉及多个基因,但不如 AD 那么强烈。复制和加强以前的报告,我们发现随着年龄变化表达的基因与 AD 中变化的基因之间存在高度显著的重叠,并且我们观察到这些变化通常在同一方向。这一结果支持正常衰老和易患 AD 的生物学过程之间的重叠,并表明与年龄相关的基因表达变化可能会增加患 AD 的风险。