APOE genotype and diet influences on Alzheimer's biomarkers

APOE 基因型和饮食对阿尔茨海默病生物标志物的影响

• 批准号: 8966525
• 负责人: Angela J Hanson
• 金额: $ 15.34万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2020-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8966525
• 关键词: Alzheimer' s Disease; Alzheimer' s disease risk; Amyloid; Amyloid beta-Protein; Animals; Apolipoprotein E; Binding; Biological Markers; Blood; Blood - brain barrier anatomy; Brain; Brain Chemistry; Cerebrospinal Fluid; Clinical Investigator; Cognition; Cognitive; Collection; Crossover Design; Diet; Dietary Fats; Elderly; Experimental Animal Model; Figs - dietary; Food; General Population; Genotype; Glucose; Glycemic Index; Goals; Health; In Vitro; Individual; Infusion procedures; Ingestion; Insulin; Insulin Resistance; K-Series Research Career Programs; Late Onset Alzheimer Disease; Link; Lipid Binding; Lipids; Measures; Mediating; Metabolic; Metabolism; Neurons; Nonesterified Fatty Acids; Participant; Pathogenesis; Patients; Peripheral; Protein Isoforms; Proteins; Recommendation; Reporting; Risk; Risk Factors; Statistical Methods; Testing; Triglycerides; Work; apolipoprotein E-4; base; cognitive testing; feeding; high risk; improved; improved functioning; insulin sensitivity; lipid transport; public health relevance; response; risk variant; saturated fat; sugar; tool; western diet

 DESCRIPTION (provided by applicant): The 'Western diet' which is characterized by high saturated fat and high glycemic index foods (high diet) is a risk factor for Alzheimer's disease (AD). However, we have found paradoxically that experimental feeding with a Western style high diet acutely improves cognition in APOE E4 carriers, who are at increased risk for AD. The purpose of this project is to examine mechanisms that underlie this response. Based on known intrinsic differences in brain chemistry in E4 carriers, we hypothesize that in this group, a high meal will result in increased brain transport of lipids and insulin, increased ApoE lipidation, increased brain amyloid clearance, and ultimately improved cognition. We will test these hypotheses by conducting a controlled meal challenge in a crossover design in older adults with both a high meal, as well as a meal low in saturated fat and glycemic index foods (low). After the meal, participants will undergo cognitive testing and collection of blood and spinal fluid for analysis of lipids, insulin, and known AD biomarkers. This work will contribute to our broader understanding about the risks of diet and AD, and how APOE genotype moderates that risk. In addition to advancing our understanding about AD pathogenesis, this career development award will give me the necessary tools to become an independent clinical investigator in the field of metabolism and Alzheimer's disease.