Retinal Mitochondrial Metabolism in Alzheimer's Disease

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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.