Retinal Mitochondrial Metabolism in Alzheimer's Disease

项目总结/摘要 阿尔茨海默病（AD）是痴呆症的主要原因。早期诊断的有效治疗和检测 仍然无法获得。AD患者通常在神经系统疾病发作之前发生眼部病变， 症状多种证据表明，代谢改变是AD的潜在机制。我们 最近发现，与线粒体相关的代谢物存在早期和常见的变化， 在具有三种常见人类突变的AD小鼠模型中，研究了脑和眼组织内的代谢。 我们的研究结果强烈表明，研究早期AD患者眼部的代谢变化可能有希望， 早期诊断AD。该项目的长期目标是确定代谢特征， 在AD的早期阶段，将眼组织与大脑进行比较，以开发新的早期生物标志物，并揭示 AD的生化基础我们计划使用最先进的技术， 技术，包括有针对性的代谢组学和代谢通量分析。 这项研究的结果将提供临床前AD中眼睛和大脑的早期代谢生物标志物， 揭示AD早期线粒体代谢的代谢流。由于眼睛很容易接近， 这一建议将为开发早期检测和潜在的新策略提供坚实的基础。 早期干预的目标。

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.