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X chromosome aneuploidy in the Alzheimer’s disease brain
BACKGROUND: Although the link between brain aging and Alzheimer’s disease (AD) is a matter of debate, processes hallmarking cellular and tissue senescence have been repeatedly associated with its pathogenesis. Here, we have studied X chromosome aneuploidy (a recognized feature of aged cell populatio...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3995993/ https://www.ncbi.nlm.nih.gov/pubmed/24602248 http://dx.doi.org/10.1186/1755-8166-7-20 |
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author | Yurov, Yuri B Vorsanova, Svetlana G Liehr, Thomas Kolotii, Alexei D Iourov, Ivan Y |
author_facet | Yurov, Yuri B Vorsanova, Svetlana G Liehr, Thomas Kolotii, Alexei D Iourov, Ivan Y |
author_sort | Yurov, Yuri B |
collection | PubMed |
description | BACKGROUND: Although the link between brain aging and Alzheimer’s disease (AD) is a matter of debate, processes hallmarking cellular and tissue senescence have been repeatedly associated with its pathogenesis. Here, we have studied X chromosome aneuploidy (a recognized feature of aged cell populations) in the AD brain. RESULTS: Extended molecular neurocytogenetic analyses of X chromosome aneuploidy in 10 female AD as well as 10 age and sex matched female control postmortem brain samples was performed by multiprobe/quantitative FISH. Additionally, aneuploidy rate in the brain samples of 5 AD and as 5 age and sex matched control subjects were analyzed by interphase chromosome-specific multicolor banding (ICS-MCB). Totally, 182,500 cells in the AD brain and 182,500 cells in the unaffected brain were analyzed. The mean rate of X chromosome aneuploidy in AD samples was approximately two times higher than in control (control: mean - 1.32%, 95% CI 0.92- 1.71%; AD: mean - 2.79%, 95% CI 1.88-3.69; P = 0.013). One AD sample demonstrated mosaic aneuploidy of chromosome X confined to the hippocampus affecting about 10% of cells. ICS-MCB confirmed the presence of X chromosome aneuploidy in the hippocampal tissues of AD brain (control: mean - 1.74%, 95% CI 1.38- 2.10%; AD: mean - 4.92%, 95% CI 1.14-8.71; P < 0.001). CONCLUSIONS: Addressing X chromosome number variation in the brain, we observed that somatically acquired (post-zygotic) aneuploidy causes large-scale genomic alterations in neural cells of AD patients and, therefore, can be involved in pathogenesis of this common neurodegenerative disorder. In the context of debates about possible interplay between brain aging and AD neurodegeneration, our findings suggest that X chromosome aneuploidy can contribute to both processes. To this end we conclude that mosaic aneuploidy in the brain is a new non-heritable genetic factor predisposing to AD. |
format | Online Article Text |
id | pubmed-3995993 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-39959932014-04-24 X chromosome aneuploidy in the Alzheimer’s disease brain Yurov, Yuri B Vorsanova, Svetlana G Liehr, Thomas Kolotii, Alexei D Iourov, Ivan Y Mol Cytogenet Research BACKGROUND: Although the link between brain aging and Alzheimer’s disease (AD) is a matter of debate, processes hallmarking cellular and tissue senescence have been repeatedly associated with its pathogenesis. Here, we have studied X chromosome aneuploidy (a recognized feature of aged cell populations) in the AD brain. RESULTS: Extended molecular neurocytogenetic analyses of X chromosome aneuploidy in 10 female AD as well as 10 age and sex matched female control postmortem brain samples was performed by multiprobe/quantitative FISH. Additionally, aneuploidy rate in the brain samples of 5 AD and as 5 age and sex matched control subjects were analyzed by interphase chromosome-specific multicolor banding (ICS-MCB). Totally, 182,500 cells in the AD brain and 182,500 cells in the unaffected brain were analyzed. The mean rate of X chromosome aneuploidy in AD samples was approximately two times higher than in control (control: mean - 1.32%, 95% CI 0.92- 1.71%; AD: mean - 2.79%, 95% CI 1.88-3.69; P = 0.013). One AD sample demonstrated mosaic aneuploidy of chromosome X confined to the hippocampus affecting about 10% of cells. ICS-MCB confirmed the presence of X chromosome aneuploidy in the hippocampal tissues of AD brain (control: mean - 1.74%, 95% CI 1.38- 2.10%; AD: mean - 4.92%, 95% CI 1.14-8.71; P < 0.001). CONCLUSIONS: Addressing X chromosome number variation in the brain, we observed that somatically acquired (post-zygotic) aneuploidy causes large-scale genomic alterations in neural cells of AD patients and, therefore, can be involved in pathogenesis of this common neurodegenerative disorder. In the context of debates about possible interplay between brain aging and AD neurodegeneration, our findings suggest that X chromosome aneuploidy can contribute to both processes. To this end we conclude that mosaic aneuploidy in the brain is a new non-heritable genetic factor predisposing to AD. BioMed Central 2014-03-06 /pmc/articles/PMC3995993/ /pubmed/24602248 http://dx.doi.org/10.1186/1755-8166-7-20 Text en Copyright © 2014 Yurov et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Yurov, Yuri B Vorsanova, Svetlana G Liehr, Thomas Kolotii, Alexei D Iourov, Ivan Y X chromosome aneuploidy in the Alzheimer’s disease brain |
title | X chromosome aneuploidy in the Alzheimer’s disease brain |
title_full | X chromosome aneuploidy in the Alzheimer’s disease brain |
title_fullStr | X chromosome aneuploidy in the Alzheimer’s disease brain |
title_full_unstemmed | X chromosome aneuploidy in the Alzheimer’s disease brain |
title_short | X chromosome aneuploidy in the Alzheimer’s disease brain |
title_sort | x chromosome aneuploidy in the alzheimer’s disease brain |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3995993/ https://www.ncbi.nlm.nih.gov/pubmed/24602248 http://dx.doi.org/10.1186/1755-8166-7-20 |
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