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Mitochondrial DNA Rearrangement Spectrum in Brain Tissue of Alzheimer’s Disease: Analysis of 13 Cases

BACKGROUND: Mitochondrial dysfunction may play a central role in the pathologic process of Alzheimer’s disease (AD), but there is still a scarcity of data that directly links the pathology of AD with the alteration of mitochondrial DNA. This study aimed to provide a comprehensive assessment of mtDNA...

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Autores principales: Chen, Yucai, Liu, Changsheng, Parker, William Davis, Chen, Hongyi, Beach, Thomas G., Liu, Xinhua, Serrano, Geidy E., Lu, Yanfen, Huang, Jianjun, Yang, Kunfang, Wang, Chunmei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4907522/
https://www.ncbi.nlm.nih.gov/pubmed/27299301
http://dx.doi.org/10.1371/journal.pone.0154582
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author Chen, Yucai
Liu, Changsheng
Parker, William Davis
Chen, Hongyi
Beach, Thomas G.
Liu, Xinhua
Serrano, Geidy E.
Lu, Yanfen
Huang, Jianjun
Yang, Kunfang
Wang, Chunmei
author_facet Chen, Yucai
Liu, Changsheng
Parker, William Davis
Chen, Hongyi
Beach, Thomas G.
Liu, Xinhua
Serrano, Geidy E.
Lu, Yanfen
Huang, Jianjun
Yang, Kunfang
Wang, Chunmei
author_sort Chen, Yucai
collection PubMed
description BACKGROUND: Mitochondrial dysfunction may play a central role in the pathologic process of Alzheimer’s disease (AD), but there is still a scarcity of data that directly links the pathology of AD with the alteration of mitochondrial DNA. This study aimed to provide a comprehensive assessment of mtDNA rearrangement events in AD brain tissue. PATIENTS AND METHODS: Postmortem frozen human brain cerebral cortex samples were obtained from the Banner Sun Health Research Institute Brain and Body Donation Program, Sun City, AZ. Mitochondria were isolated and direct sequence by using MiSeq®, and analyzed by relative software. RESULTS: Three types of mitochondrial DNA (mtDNA) rearrangements have been seen in post mortem human brain tissue from patients with AD and age matched control. These observed rearrangements include a deletion, F-type rearrangement, and R-type rearrangement. We detected a high level of mtDNA rearrangement in brain tissue from cognitively normal subjects, as well as the patients with Alzheimer's disease (AD). The rate of rearrangements was calculated by dividing the number of positive rearrangements by the coverage depth. The rearrangement rate was significantly higher in AD brain tissue than in control brain tissue (17.9%versus 6.7%; p = 0.0052). Of specific types of rearrangement, deletions were markedly increased in AD (9.2% versus 2.3%; p = 0.0005). CONCLUSIONS: Our data showed that failure of mitochondrial DNA in AD brain might be important etiology of AD pathology.
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spelling pubmed-49075222016-07-18 Mitochondrial DNA Rearrangement Spectrum in Brain Tissue of Alzheimer’s Disease: Analysis of 13 Cases Chen, Yucai Liu, Changsheng Parker, William Davis Chen, Hongyi Beach, Thomas G. Liu, Xinhua Serrano, Geidy E. Lu, Yanfen Huang, Jianjun Yang, Kunfang Wang, Chunmei PLoS One Research Article BACKGROUND: Mitochondrial dysfunction may play a central role in the pathologic process of Alzheimer’s disease (AD), but there is still a scarcity of data that directly links the pathology of AD with the alteration of mitochondrial DNA. This study aimed to provide a comprehensive assessment of mtDNA rearrangement events in AD brain tissue. PATIENTS AND METHODS: Postmortem frozen human brain cerebral cortex samples were obtained from the Banner Sun Health Research Institute Brain and Body Donation Program, Sun City, AZ. Mitochondria were isolated and direct sequence by using MiSeq®, and analyzed by relative software. RESULTS: Three types of mitochondrial DNA (mtDNA) rearrangements have been seen in post mortem human brain tissue from patients with AD and age matched control. These observed rearrangements include a deletion, F-type rearrangement, and R-type rearrangement. We detected a high level of mtDNA rearrangement in brain tissue from cognitively normal subjects, as well as the patients with Alzheimer's disease (AD). The rate of rearrangements was calculated by dividing the number of positive rearrangements by the coverage depth. The rearrangement rate was significantly higher in AD brain tissue than in control brain tissue (17.9%versus 6.7%; p = 0.0052). Of specific types of rearrangement, deletions were markedly increased in AD (9.2% versus 2.3%; p = 0.0005). CONCLUSIONS: Our data showed that failure of mitochondrial DNA in AD brain might be important etiology of AD pathology. Public Library of Science 2016-06-14 /pmc/articles/PMC4907522/ /pubmed/27299301 http://dx.doi.org/10.1371/journal.pone.0154582 Text en © 2016 Chen et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Chen, Yucai
Liu, Changsheng
Parker, William Davis
Chen, Hongyi
Beach, Thomas G.
Liu, Xinhua
Serrano, Geidy E.
Lu, Yanfen
Huang, Jianjun
Yang, Kunfang
Wang, Chunmei
Mitochondrial DNA Rearrangement Spectrum in Brain Tissue of Alzheimer’s Disease: Analysis of 13 Cases
title Mitochondrial DNA Rearrangement Spectrum in Brain Tissue of Alzheimer’s Disease: Analysis of 13 Cases
title_full Mitochondrial DNA Rearrangement Spectrum in Brain Tissue of Alzheimer’s Disease: Analysis of 13 Cases
title_fullStr Mitochondrial DNA Rearrangement Spectrum in Brain Tissue of Alzheimer’s Disease: Analysis of 13 Cases
title_full_unstemmed Mitochondrial DNA Rearrangement Spectrum in Brain Tissue of Alzheimer’s Disease: Analysis of 13 Cases
title_short Mitochondrial DNA Rearrangement Spectrum in Brain Tissue of Alzheimer’s Disease: Analysis of 13 Cases
title_sort mitochondrial dna rearrangement spectrum in brain tissue of alzheimer’s disease: analysis of 13 cases
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4907522/
https://www.ncbi.nlm.nih.gov/pubmed/27299301
http://dx.doi.org/10.1371/journal.pone.0154582
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