Rebeck G William
Department of Neuroscience, Georgetown University Medical Center, Washington, DC.
J Lipid Res. 2017 Aug;58(8):1493-1499. doi: 10.1194/jlr.R075408. Epub 2017 Mar 2.
The role of APOE in the risk of Alzheimer's disease (AD) has largely focused on its effects on AD pathological processes. However, there are increasing data that genotype affects processes in normal brains. Studies of young cognitively normal humans show effects of genotype on brain structure and activity. Studies of normal knock-in mice show effects of genotype on brain structure, neuronal markers, and behavior. APOE interactions with molecules important for lipid efflux and lipid endocytosis underlie effects of genotype on neuroinflammation and lipoprotein composition. These effects provide important targets for new therapies for reduction of the risk of AD before any signs of pathogenesis.
APOE在阿尔茨海默病（AD）风险中的作用主要集中在其对AD病理过程的影响上。然而，越来越多的数据表明，基因型会影响正常大脑中的各种过程。对认知正常的年轻人的研究显示，基因型对大脑结构和活动有影响。对正常基因敲入小鼠的研究表明，基因型对大脑结构、神经元标志物和行为有影响。APOE与脂质外流和脂质内吞作用重要分子的相互作用是基因型对神经炎症和脂蛋白组成产生影响的基础。这些影响为在发病机制出现任何迹象之前降低AD风险的新疗法提供了重要靶点。
