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

APOE 基因型对人脑甘油三酯和血流的影响

• 批准号: 10565889
• 负责人: Angela J Hanson
• 金额: $ 45.12万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10565889
• 关键词: Acute; Alleles; Alzheimer' s Disease; Alzheimer' s disease risk; Animals; Area; Blood Pressure; Blood flow; Body Composition; Brain; Brain region; Cerebrospinal Fluid; Cerebrovascular Circulation; Cerebrum; Clinical Research; Cognition; Cognitive; Coupled; Dairy Products; Dairying; Diet; Drops; Dual-Energy X-Ray Absorptiometry; Elderly; Enrollment; Exhibits; Fasting; Fatty acid glycerol esters; Feeling; Genes; Genotype; Glucose; Glucose Intolerance; Glycosylated hemoglobin A; Hour; Human; Image; Individual; Ingestion; Insulin; Intervention; Investigation; Laboratories; Lipids; Liquid substance; Magnetic Resonance Imaging; Measures; Metabolic; Metabolic Marker; Metabolic Pathway; Metabolic syndrome; Metabolism; Methods; OGTT; Oral; Participant; Pathogenesis; Pathogenicity; Pathway interactions; Peripheral; Persons; Play; Risk; Role; Sampling; Satiation; Spinal Puncture; Systemic blood pressure; Techniques; Technology; Testing; Triglycerides; United States National Institutes of Health; apolipoprotein E-4; arterial spin labeling; brain metabolism; cognitive testing; experimental study; feeding; glucose tolerance; high risk; improved; lipidomics; metabolic profile; metabolomics; nutrient metabolism; predictive marker; primary outcome; regional difference; response; risk variant; secondary analysis; western diet

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.

7.项目摘要 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APOE ε4（E4）的个体对高脂饮食（HFF）的反应不同， 几种代谢和认知反应的术语。我们提出的证据表明，动脉自旋标记（ASL）MRI 是评价急性期全脑和局部脑血流量（CBF）变化的一种有效的无创性方法。 我们将提出一项老年人的临床研究，包括摄入高脂肪饮料，以测试预测， 与禁食相比，E4携带者对HFF的反应将显示更高的CBF，而E4非携带者将显示 降低CBF。我们将进一步研究区域差异，重点是已知的大脑区域， 参与AD发病机制，我们将对所有参与者进行认知测试， CBF和认知的流体测量之间的关系。在此建议中，我们还将调查外围设备是否 葡萄糖耐量和身体成分的代谢指标可预测E4水平是否升高， 影响这些预测。该干预将与脂质组学和代谢组学分析同时进行 一项正在进行的老年人研究中，老年人在摄入含有类似脂质的高脂肪餐后， 满足于高脂肪饮料。通过这些研究，我们希望能够更深入地了解HFF如何 对E4携带者和非携带者的脑功能和代谢产生影响，并识别脑区 其特别易受HFF的急性作用的影响。