Retinal Mitochondrial Metabolism in Alzheimer's Disease

阿尔茨海默病的视网膜线粒体代谢

• 批准号: 10707698
• 负责人: Jianhai Du
• 金额: $ 38万
• 依托单位: WEST VIRGINIA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-01 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10707698
• 关键词: 3xTg-AD mouse; Age Months; Age related macular degeneration; Alzheimer' s Disease; Alzheimer' s disease diagnosis; Alzheimer' s disease patient; Animal Disease Models; Animals; Biochemical; Bioenergetics; Biological Markers; Brain; Coenzyme A; Data; Defect; Dementia; Early Diagnosis; Early Intervention; Early identification; Early treatment; Enzymes; Eye; Female; Foundations; Genes; Goals; Human; In Vitro; Incidence; Literature; Measures; Metabolic; Metabolic dysfunction; Metabolism; Mitochondria; Mus; Mutation; Neurologic Symptoms; Nutrient; Ocular Pathology; Outcomes Research; Pathogenesis; Pathologic; Pathology; Pathway interactions; Reaction; Retina; Retinal Degeneration; Source; Structure of retinal pigment epithelium; Symptoms; Technology; Testing; Tissues; Tracer; Transgenic Mice; Translating; Visual; Visual System; brain metabolism; early detection biomarkers; effective therapy; in vivo; metabolic abnormality assessment; metabolome; metabolomics; mitochondrial metabolism; mouse model; neural; novel strategies; pre-clinical; reaction rate; sex; stable isotope

PROJECT SUMMARY/ABSTRACT Alzheimer’s disease (AD) is the leading cause of dementia. Effective treatment and tests for early diagnosis are still not available. AD patients often have ocular pathology occurring before the onset of neurological symptoms. Multiple lines of evidence show that altered metabolism is the underlying mechanism for AD. We recently found that there are early and common changes in metabolites associated with mitochondrial metabolism within brain and eye tissues in an AD mouse model harboring three common human mutations. Our findings strongly suggest that studying metabolic changes in the eye of early AD could be promising to develop an earlier diagnosis for AD. The long-term goal of this project is to identify the metabolic signature of eye tissues compared to the brain in the early stage of AD to develop new early biomarkers and to reveal the biochemical basis of AD. We plan to rigorously investigate the changes of metabolome using state-of-the-art technologies, including targeted metabolomics and metabolic flux analysis. The outcome of this research will provide early metabolic biomarkers in the eye and brain in preclinical AD, reveal the metabolic flux in mitochondrial metabolism in early AD. As the eye is easily accessible, the findings of this proposal will provide a strong foundation to develop novel strategies for early detection and potential targets for early intervention.

项目摘要/摘要 阿尔茨海默病(AD)是导致痴呆症的主要原因。早期诊断的有效治疗和检测 仍然不可用。AD患者的眼部病变通常发生在神经性疾病发作之前 症状。多条证据表明，新陈代谢改变是AD的潜在机制。我们 最近发现，与线粒体有关的代谢物存在早期和常见的变化 携带三种常见人类突变的AD小鼠模型的脑和眼组织中的新陈代谢。 我们的发现有力地表明，研究早期阿尔茨海默病患者眼睛的代谢变化可能有希望 开发AD的早期诊断。该项目的长期目标是确定 比较眼组织和脑组织在AD早期开发新的早期生物标志物和揭示 AD的生化基础。我们计划使用最先进的技术严格研究代谢组的变化 技术，包括靶向代谢组学和代谢通量分析。 这项研究的结果将为临床前AD患者的眼睛和大脑提供早期代谢生物标志物。 揭示AD早期线粒体代谢的代谢通量。由于眼睛很容易接触到，这些发现 这一提议将为开发早期发现和潜在的新战略提供坚实的基础 早期干预的目标。