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APOE Locus-Associated Mitochondrial Function and Its Implication in Alzheimer’s Disease and Aging

The Apolipoprotein E (APOE) locus has garnered significant clinical interest because of its association with Alzheimer’s disease (AD) and longevity. This genetic association appears across multiple genes in the APOE locus. Despite the apparent differences between AD and longevity, both conditions sh...

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Autores principales: Lee, Eun-Gyung, Leong, Lesley, Chen, Sunny, Tulloch, Jessica, Yu, Chang-En
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10341489/
https://www.ncbi.nlm.nih.gov/pubmed/37445616
http://dx.doi.org/10.3390/ijms241310440
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author Lee, Eun-Gyung
Leong, Lesley
Chen, Sunny
Tulloch, Jessica
Yu, Chang-En
author_facet Lee, Eun-Gyung
Leong, Lesley
Chen, Sunny
Tulloch, Jessica
Yu, Chang-En
author_sort Lee, Eun-Gyung
collection PubMed
description The Apolipoprotein E (APOE) locus has garnered significant clinical interest because of its association with Alzheimer’s disease (AD) and longevity. This genetic association appears across multiple genes in the APOE locus. Despite the apparent differences between AD and longevity, both conditions share a commonality of aging-related changes in mitochondrial function. This commonality is likely due to accumulative biological effects partly exerted by the APOE locus. In this study, we investigated changes in mitochondrial structure/function-related markers using oxidative stress-induced human cellular models and postmortem brains (PMBs) from individuals with AD and normal controls. Our results reveal a range of expressional alterations, either upregulated or downregulated, in these genes in response to oxidative stress. In contrast, we consistently observed an upregulation of multiple APOE locus genes in all cellular models and AD PMBs. Additionally, the effects of AD status on mitochondrial DNA copy number (mtDNA CN) varied depending on APOE genotype. Our findings imply a potential coregulation of APOE locus genes possibly occurring within the same topologically associating domain (TAD) of the 3D chromosome conformation. The coordinated expression of APOE locus genes could impact mitochondrial function, contributing to the development of AD or longevity. Our study underscores the significant role of the APOE locus in modulating mitochondrial function and provides valuable insights into the underlying mechanisms of AD and aging, emphasizing the importance of this locus in clinical research.
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spelling pubmed-103414892023-07-14 APOE Locus-Associated Mitochondrial Function and Its Implication in Alzheimer’s Disease and Aging Lee, Eun-Gyung Leong, Lesley Chen, Sunny Tulloch, Jessica Yu, Chang-En Int J Mol Sci Article The Apolipoprotein E (APOE) locus has garnered significant clinical interest because of its association with Alzheimer’s disease (AD) and longevity. This genetic association appears across multiple genes in the APOE locus. Despite the apparent differences between AD and longevity, both conditions share a commonality of aging-related changes in mitochondrial function. This commonality is likely due to accumulative biological effects partly exerted by the APOE locus. In this study, we investigated changes in mitochondrial structure/function-related markers using oxidative stress-induced human cellular models and postmortem brains (PMBs) from individuals with AD and normal controls. Our results reveal a range of expressional alterations, either upregulated or downregulated, in these genes in response to oxidative stress. In contrast, we consistently observed an upregulation of multiple APOE locus genes in all cellular models and AD PMBs. Additionally, the effects of AD status on mitochondrial DNA copy number (mtDNA CN) varied depending on APOE genotype. Our findings imply a potential coregulation of APOE locus genes possibly occurring within the same topologically associating domain (TAD) of the 3D chromosome conformation. The coordinated expression of APOE locus genes could impact mitochondrial function, contributing to the development of AD or longevity. Our study underscores the significant role of the APOE locus in modulating mitochondrial function and provides valuable insights into the underlying mechanisms of AD and aging, emphasizing the importance of this locus in clinical research. MDPI 2023-06-21 /pmc/articles/PMC10341489/ /pubmed/37445616 http://dx.doi.org/10.3390/ijms241310440 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lee, Eun-Gyung
Leong, Lesley
Chen, Sunny
Tulloch, Jessica
Yu, Chang-En
APOE Locus-Associated Mitochondrial Function and Its Implication in Alzheimer’s Disease and Aging
title APOE Locus-Associated Mitochondrial Function and Its Implication in Alzheimer’s Disease and Aging
title_full APOE Locus-Associated Mitochondrial Function and Its Implication in Alzheimer’s Disease and Aging
title_fullStr APOE Locus-Associated Mitochondrial Function and Its Implication in Alzheimer’s Disease and Aging
title_full_unstemmed APOE Locus-Associated Mitochondrial Function and Its Implication in Alzheimer’s Disease and Aging
title_short APOE Locus-Associated Mitochondrial Function and Its Implication in Alzheimer’s Disease and Aging
title_sort apoe locus-associated mitochondrial function and its implication in alzheimer’s disease and aging
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10341489/
https://www.ncbi.nlm.nih.gov/pubmed/37445616
http://dx.doi.org/10.3390/ijms241310440
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