权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

The delivery of essential fatty acids to the Brain in Alzheimer's disease

向阿尔茨海默病患者的大脑输送必需脂肪酸

基本信息

批准号：
10425137
负责人：
Hussein N Yassine
金额：
$ 112.98万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-01 至 2023-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10425137
关键词：
Abeta clearance Adult Age Albumins Alleles Alzheimer&apos s Disease Alzheimer&apos s disease brain Alzheimer&apos s disease pathology Alzheimer&apos s disease risk Amyloid beta-42 Animal Model Apolipoprotein E Biological Markers Biometry Blood - brain barrier anatomy Brain Brain imaging COVID-19 pandemic Cerebrospinal Fluid Clinical Trials Cognition Cognitive Collaborations Defect Dementia Disease Docosahexaenoic Acids Docosahexaenoic acid supplementation Dose Double-Blind Method Dropout Erythrocytes Essential Fatty Acids Functional Magnetic Resonance Imaging Funding Genotype Goals High Density Lipoproteins Human Impaired cognition Incidence Individual Laws Lipoproteins Maintenance Measures Mediating Membrane Metabolism Mus Neurons Nutrient Omega-3 Fatty Acids Outcome Participant Peripheral Persons Phase III Clinical Trials Phospholipase A2 Placebos Plasma Population Production Public Health Randomized Randomized Clinical Trials Reporting Research Rest Risk Rodent Structure Subgroup Supplementation Synaptic plasticity Target Populations Transgenic Mice apolipoprotein E-4 cognitive change cognitive function cost cost effective effective therapy genetic risk factor human old age (65+)mouse model non-demented novel preservation prevent primary outcome programs recruit response secondary outcome therapy development week trial

项目摘要

Our studies suggest that APOE4 carriers have abnormalities in brain DHA metabolism that precede the onset of Alzheimer’s disease (AD) dementia. Early and long-term high dose DHA supplementation in APOE4 animal models preserves cognitive functions. Subgroup analyses of several randomized clinical trials suggest that APOE4 carriers may benefit for omega 3 supplementation prior to the onset of AD. In the DHA Brain Delivery Trial (R01AG054434) we are studying the effect of APOE4 on the response to DHA supplementation in 160 non-demented adults randomized to 2 grams of DHA daily vs placebo for over 2 years. The goal of DHA brain delivery study is to determine the effect of APOE genotype on brain DHA levels (using cerebrospinal fluid, primary outcome), on brain volumetric and functional connectivity change (secondary outcomes) and cognition (exploratory outcomes) after DHA supplementation, providing novel information on mechanisms for APOE4 mediated AD risk. We are requesting supplemental close out funds to cover unanticipated increase in costs due to the COVID-19 pandemic that resulted in greater participant drop-out rates and recruitment delays during 2020-2021.

我们的研究表明，APOE 4携带者的大脑DHA代谢异常，在阿尔茨海默病（AD）痴呆症发作之前。早期和长期高剂量DHA 在APOE 4动物模型中补充APOE 4可保留认知功能。的亚组分析几项随机临床试验表明，APOE 4携带者可能受益于欧米茄3，在AD发作之前补充。在DHA脑递送试验（R 01 AG 054434）中，我们正在研究APOE 4对 160名非痴呆成年人随机接受2克DHA补充剂的反应每天一次，与安慰剂相比，持续2年以上。DHA脑递送研究的目标是确定 APOE基因型对脑DHA水平的影响（使用脑脊液，主要结果），脑容量和功能连接变化（次要结局）和认知（探索性结果）补充DHA后，提供有关机制的新信息 APOE 4介导的AD风险。我们正在申请补充关闭资金，以支付由于以下原因而导致的意外成本增加 2019冠状病毒病大流行导致参与者辍学率和招募人数增加 2020-2021年期间延迟。