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，APOE4载体在脑DHA代谢中具有异常在阿尔茨海默氏病（AD）痴呆的发作之前。早期和长期高剂量DHA APOE4动物模型中的补充可保留认知功能。亚组分析几项随机临床试验表明，APOE4载体可能受益于Omega 3 在AD发作之前补充。在DHA脑输送试验（R01AG054434）中，我们正在研究APOE4对对160名随机分配至2克DHA的160名非痴呆成年人的DHA补充的响应每日与安慰剂超过2年。 DHA脑输送研究的目的是确定 APOE基因型对脑DHA水平的影响（使用脑脊液，主要结局），对大脑容量和功能连通性变化（次要结果）和认知（探索结果）补充DHA后，提供有关机制的新信息对于APOE4中介AD风险。我们要求补充封闭资金，以支付由于导致更多参与辍学率和招募的共同19-19大流行 2020-2021期间的延误。