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Differential DNA Methylation in the Brain as Potential Mediator of the Association between Traffic-related PM(2.5) and Neuropathology Markers of Alzheimer’s Disease
INTRODUCTION: Growing evidence indicates fine particulate matter (PM(2.5)) as risk factor for Alzheimer’s’ disease (AD), but the underlying mechanisms have been insufficiently investigated. We hypothesized differential DNA methylation (DNAm) in brain tissue as potential mediator of this association....
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10327281/ https://www.ncbi.nlm.nih.gov/pubmed/37425713 http://dx.doi.org/10.1101/2023.06.30.23292085 |
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author | Li, Zhenjiang Liang, Donghai Ebelt, Stefanie Gearing, Marla Kobor, Michael S. Konwar, Chaini Maclsaac, Julie L Dever, Kristy Wingo, Aliza Levey, Allan Lah, James J. Wingo, Thomas Huels, Anke |
author_facet | Li, Zhenjiang Liang, Donghai Ebelt, Stefanie Gearing, Marla Kobor, Michael S. Konwar, Chaini Maclsaac, Julie L Dever, Kristy Wingo, Aliza Levey, Allan Lah, James J. Wingo, Thomas Huels, Anke |
author_sort | Li, Zhenjiang |
collection | PubMed |
description | INTRODUCTION: Growing evidence indicates fine particulate matter (PM(2.5)) as risk factor for Alzheimer’s’ disease (AD), but the underlying mechanisms have been insufficiently investigated. We hypothesized differential DNA methylation (DNAm) in brain tissue as potential mediator of this association. METHODS: We assessed genome-wide DNAm (Illumina EPIC BeadChips) in prefrontal cortex tissue and three AD-related neuropathological markers (Braak stage, CERAD, ABC score) for 159 donors, and estimated donors’ residential traffic-related PM(2.5) exposure 1, 3 and 5 years prior to death. We used a combination of the Meet-in-the-Middle approach, high-dimensional mediation analysis, and causal mediation analysis to identify potential mediating CpGs. RESULTS: PM(2.5) was significantly associated with differential DNAm at cg25433380 and cg10495669. Twenty-six CpG sites were identified as mediators of the association between PM(2.5) exposure and neuropathology markers, several located in genes related to neuroinflammation. DISCUSSION: Our findings suggest differential DNAm related to neuroinflammation mediates the association between traffic-related PM(2.5) and AD. |
format | Online Article Text |
id | pubmed-10327281 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
spelling | pubmed-103272812023-07-08 Differential DNA Methylation in the Brain as Potential Mediator of the Association between Traffic-related PM(2.5) and Neuropathology Markers of Alzheimer’s Disease Li, Zhenjiang Liang, Donghai Ebelt, Stefanie Gearing, Marla Kobor, Michael S. Konwar, Chaini Maclsaac, Julie L Dever, Kristy Wingo, Aliza Levey, Allan Lah, James J. Wingo, Thomas Huels, Anke medRxiv Article INTRODUCTION: Growing evidence indicates fine particulate matter (PM(2.5)) as risk factor for Alzheimer’s’ disease (AD), but the underlying mechanisms have been insufficiently investigated. We hypothesized differential DNA methylation (DNAm) in brain tissue as potential mediator of this association. METHODS: We assessed genome-wide DNAm (Illumina EPIC BeadChips) in prefrontal cortex tissue and three AD-related neuropathological markers (Braak stage, CERAD, ABC score) for 159 donors, and estimated donors’ residential traffic-related PM(2.5) exposure 1, 3 and 5 years prior to death. We used a combination of the Meet-in-the-Middle approach, high-dimensional mediation analysis, and causal mediation analysis to identify potential mediating CpGs. RESULTS: PM(2.5) was significantly associated with differential DNAm at cg25433380 and cg10495669. Twenty-six CpG sites were identified as mediators of the association between PM(2.5) exposure and neuropathology markers, several located in genes related to neuroinflammation. DISCUSSION: Our findings suggest differential DNAm related to neuroinflammation mediates the association between traffic-related PM(2.5) and AD. Cold Spring Harbor Laboratory 2023-06-30 /pmc/articles/PMC10327281/ /pubmed/37425713 http://dx.doi.org/10.1101/2023.06.30.23292085 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. |
spellingShingle | Article Li, Zhenjiang Liang, Donghai Ebelt, Stefanie Gearing, Marla Kobor, Michael S. Konwar, Chaini Maclsaac, Julie L Dever, Kristy Wingo, Aliza Levey, Allan Lah, James J. Wingo, Thomas Huels, Anke Differential DNA Methylation in the Brain as Potential Mediator of the Association between Traffic-related PM(2.5) and Neuropathology Markers of Alzheimer’s Disease |
title | Differential DNA Methylation in the Brain as Potential Mediator of the Association between Traffic-related PM(2.5) and Neuropathology Markers of Alzheimer’s Disease |
title_full | Differential DNA Methylation in the Brain as Potential Mediator of the Association between Traffic-related PM(2.5) and Neuropathology Markers of Alzheimer’s Disease |
title_fullStr | Differential DNA Methylation in the Brain as Potential Mediator of the Association between Traffic-related PM(2.5) and Neuropathology Markers of Alzheimer’s Disease |
title_full_unstemmed | Differential DNA Methylation in the Brain as Potential Mediator of the Association between Traffic-related PM(2.5) and Neuropathology Markers of Alzheimer’s Disease |
title_short | Differential DNA Methylation in the Brain as Potential Mediator of the Association between Traffic-related PM(2.5) and Neuropathology Markers of Alzheimer’s Disease |
title_sort | differential dna methylation in the brain as potential mediator of the association between traffic-related pm(2.5) and neuropathology markers of alzheimer’s disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10327281/ https://www.ncbi.nlm.nih.gov/pubmed/37425713 http://dx.doi.org/10.1101/2023.06.30.23292085 |
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