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Mapping key mitochondrial genes in Alzheimer's disease through human tissue and iPSC derived neurons.

Daiyun Dong·Waqar Ahmed·Ram Sagar·Rachel J Boyd·Vasiliki Mahairaki
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Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative condition that has become a global health challenge due to an aging world population and no available effective treatment. Mitochondrial dysfunction plays a crucial role in the development of AD due to its critical role in neuronal survival and function. However, the specific mitochondrial genes and pathways involved in AD pathogenesis remain poorly defined. In this study, we incorporated seven AD human postmortem and three AD iPSC-derived neurons (iNs) gene expression datasets to identify mitochondria-related Differentially Expressed Genes (mitoDEGs) between AD and control. The Gene Ontology (GO) analysis is conducted to investigate the AD biological mechanisms, and a random forest model is developed to assess how well the key mitoDEGs differentiate AD and control groups. Through our analysis, we identified fourteen key mitochondria related genes that show significant dysregulation in both postmortem brain tissues and iNs derived from AD patients. These genes have strong connections to oxidative stress, indicating mitochondrial dysfunction plays a crucial role in Alzheimer's disease pathology. Our study identified the key genes and pathways as promising targets for future research and therapeutic interventions, highlighting the importance of mitigating oxidative stress and restoring mitochondrial function in AD.

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HumansAlzheimer DiseaseInduced Pluripotent Stem CellsNeuronsMitochondriaGenes, MitochondrialOxidative StressGene Expression ProfilingGene OntologyBrainAlzheimer diseaseAutopsyInduced pluripotent stem cellsReactive oxygen speciesJournal ArticleResearch Support, Non-U.S. Gov'tResearch Support, N.I.H., Extramural

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Daiyun Dong, Waqar Ahmed, Ram Sagar, Rachel J Boyd, Vasiliki Mahairaki. 2025-11-28. Mapping key mitochondrial genes in Alzheimer's disease through human tissue and iPSC derived neurons.. https://doi.org/10.1038/s41598-025-27019-4

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