APOE genotype effects on triglycerides and blood flow in the human brain

7.项目总结 以高脂饮食(HFF)为特征的西方饮食是阿尔茨海默病(AD)的危险因素。 然而，携带AD风险基因apoEε4(E4)的个体对高脂喂养的反应不同。 一些新陈代谢和认知反应的术语。我们提出了动脉自旋标记(ASL)磁共振成像的证据 是一种有效的无创性评价急性全脑和局部脑血流量(∆)变化的方法。 我们将提议在老年人中进行一项涉及摄入高脂肪饮料的临床研究，以测试这一预测 与空腹相比，E4携带者对HFF的反应将表现出更高的CBF，而E4非携带者将显示 降低脑血流量。我们将进一步研究∆脑血流的地区差异，重点放在已知的大脑区域 参与了AD的发病机制，我们将对所有参与者进行认知测试，以探索两者之间的关系 CBF和流畅的认知指标之间的差异。有了这项建议，我们还将调查外围设备 糖耐量和身体成分的代谢测量可以预测∆的脑血流量，以及E4状态 会影响这些预测。这项干预将与脂组和代谢组分析并行进行。 一项正在进行的老年人摄入类似脂肪的高脂肪餐后脑脊液的研究 满足于高脂肪饮料。通过这些研究，我们希望更深入地了解HFF是如何 对E4携带者和非携带者的大脑功能和代谢产生影响，并识别大脑区域 它们特别容易受到HFF的急性影响。

7. PROJECT SUMMARY The 'Western diet' characterized by high fat feeding (HFF) is a risk factor for Alzheimer's disease (AD). However, individuals who carry the AD risk gene APOE ε4 (E4) respond differently to high fat feeding (HFF) in terms of several metabolic and cognitive responses. We present evidence that arterial spin labeling (ASL) MRI is an effective non-invasive method to evaluate acute changes in total and regional cerebral blood flow (∆CBF). We will propose a clinical study in older adults involving ingestion of a high fat drink to test the prediction that E4 carriers will show higher CBF in response to HFF compared to fasting, whereas E4 non-carriers will show lower CBF. We will further examine regional differences in ∆CBF with emphasis on brain regions known to be involved in AD pathogenesis, and we will conduct cognitive testing on all participants to explore relationships between CBF and fluid measures of cognition. With this proposal we will also investigate whether peripheral metabolic measures of glucose tolerance and body composition predict ∆CBF, and whether E4 status influences those predictions. This intervention will be done in parallel with lipidomic and metabolomic analyses of cerebrospinal fluid from an ongoing study of older adults after ingestion of a high fat meal with similar lipid content to the high fat drink. With these studies we hope to gain a more in-depth understanding of how HFF exerts influence on brain function and metabolism for E4 carriers and non-carriers, and identify brain regions which are particularly vulnerable to the acute effects of HFF.