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 携带者大脑 DHA 代谢异常在阿尔茨海默氏病 (AD) 痴呆症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。多项随机临床试验表明 APOE4 携带者可能受益于 omega 3 AD 发病前补充。在 DHA 大脑递送试验 (R01AG054434) 中，我们正在研究 APOE4 对 160 名非痴呆成年人随机服用 2 克 DHA 对补充 DHA 的反应每日与安慰剂对比 2 年以上 DHA 大脑输送研究的目标是确定 APOE 基因型对大脑 DHA 水平的影响（使用脑脊液，主要结果）大脑体积和功能连接的变化（次要结果）和认知（探索性结果）补充 DHA 后，提供有关机制的新信息 APOE4 介导的 AD 风险。我们正在请求补充结清资金，以弥补由于以下原因导致的意外成本增加： COVID-19 大流行导致参与者退出率和招募率增加 2020-2021 年期间出现延误。