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Large-scale deep multi-layer analysis of Alzheimer’s disease brain reveals strong proteomic disease-related changes not observed at the RNA level
The biological processes that are disrupted in the Alzheimer’s disease (AD) brain remain incompletely understood. In this study, we analyzed the proteomes of more than 1,000 brain tissues to reveal new AD-related protein co-expression modules that were highly preserved across cohorts and brain regio...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group US
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8825285/ https://www.ncbi.nlm.nih.gov/pubmed/35115731 http://dx.doi.org/10.1038/s41593-021-00999-y |
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author | Johnson, Erik C. B. Carter, E. Kathleen Dammer, Eric B. Duong, Duc M. Gerasimov, Ekaterina S. Liu, Yue Liu, Jiaqi Betarbet, Ranjita Ping, Lingyan Yin, Luming Serrano, Geidy E. Beach, Thomas G. Peng, Junmin De Jager, Philip L. Haroutunian, Vahram Zhang, Bin Gaiteri, Chris Bennett, David A. Gearing, Marla Wingo, Thomas S. Wingo, Aliza P. Lah, James J. Levey, Allan I. Seyfried, Nicholas T. |
author_facet | Johnson, Erik C. B. Carter, E. Kathleen Dammer, Eric B. Duong, Duc M. Gerasimov, Ekaterina S. Liu, Yue Liu, Jiaqi Betarbet, Ranjita Ping, Lingyan Yin, Luming Serrano, Geidy E. Beach, Thomas G. Peng, Junmin De Jager, Philip L. Haroutunian, Vahram Zhang, Bin Gaiteri, Chris Bennett, David A. Gearing, Marla Wingo, Thomas S. Wingo, Aliza P. Lah, James J. Levey, Allan I. Seyfried, Nicholas T. |
author_sort | Johnson, Erik C. B. |
collection | PubMed |
description | The biological processes that are disrupted in the Alzheimer’s disease (AD) brain remain incompletely understood. In this study, we analyzed the proteomes of more than 1,000 brain tissues to reveal new AD-related protein co-expression modules that were highly preserved across cohorts and brain regions. Nearly half of the protein co-expression modules, including modules significantly altered in AD, were not observed in RNA networks from the same cohorts and brain regions, highlighting the proteopathic nature of AD. Two such AD-associated modules unique to the proteomic network included a module related to MAPK signaling and metabolism and a module related to the matrisome. The matrisome module was influenced by the APOE ε4 allele but was not related to the rate of cognitive decline after adjustment for neuropathology. By contrast, the MAPK/metabolism module was strongly associated with the rate of cognitive decline. Disease-associated modules unique to the proteome are sources of promising therapeutic targets and biomarkers for AD. |
format | Online Article Text |
id | pubmed-8825285 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group US |
record_format | MEDLINE/PubMed |
spelling | pubmed-88252852022-02-18 Large-scale deep multi-layer analysis of Alzheimer’s disease brain reveals strong proteomic disease-related changes not observed at the RNA level Johnson, Erik C. B. Carter, E. Kathleen Dammer, Eric B. Duong, Duc M. Gerasimov, Ekaterina S. Liu, Yue Liu, Jiaqi Betarbet, Ranjita Ping, Lingyan Yin, Luming Serrano, Geidy E. Beach, Thomas G. Peng, Junmin De Jager, Philip L. Haroutunian, Vahram Zhang, Bin Gaiteri, Chris Bennett, David A. Gearing, Marla Wingo, Thomas S. Wingo, Aliza P. Lah, James J. Levey, Allan I. Seyfried, Nicholas T. Nat Neurosci Resource The biological processes that are disrupted in the Alzheimer’s disease (AD) brain remain incompletely understood. In this study, we analyzed the proteomes of more than 1,000 brain tissues to reveal new AD-related protein co-expression modules that were highly preserved across cohorts and brain regions. Nearly half of the protein co-expression modules, including modules significantly altered in AD, were not observed in RNA networks from the same cohorts and brain regions, highlighting the proteopathic nature of AD. Two such AD-associated modules unique to the proteomic network included a module related to MAPK signaling and metabolism and a module related to the matrisome. The matrisome module was influenced by the APOE ε4 allele but was not related to the rate of cognitive decline after adjustment for neuropathology. By contrast, the MAPK/metabolism module was strongly associated with the rate of cognitive decline. Disease-associated modules unique to the proteome are sources of promising therapeutic targets and biomarkers for AD. Nature Publishing Group US 2022-02-03 2022 /pmc/articles/PMC8825285/ /pubmed/35115731 http://dx.doi.org/10.1038/s41593-021-00999-y Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Resource Johnson, Erik C. B. Carter, E. Kathleen Dammer, Eric B. Duong, Duc M. Gerasimov, Ekaterina S. Liu, Yue Liu, Jiaqi Betarbet, Ranjita Ping, Lingyan Yin, Luming Serrano, Geidy E. Beach, Thomas G. Peng, Junmin De Jager, Philip L. Haroutunian, Vahram Zhang, Bin Gaiteri, Chris Bennett, David A. Gearing, Marla Wingo, Thomas S. Wingo, Aliza P. Lah, James J. Levey, Allan I. Seyfried, Nicholas T. Large-scale deep multi-layer analysis of Alzheimer’s disease brain reveals strong proteomic disease-related changes not observed at the RNA level |
title | Large-scale deep multi-layer analysis of Alzheimer’s disease brain reveals strong proteomic disease-related changes not observed at the RNA level |
title_full | Large-scale deep multi-layer analysis of Alzheimer’s disease brain reveals strong proteomic disease-related changes not observed at the RNA level |
title_fullStr | Large-scale deep multi-layer analysis of Alzheimer’s disease brain reveals strong proteomic disease-related changes not observed at the RNA level |
title_full_unstemmed | Large-scale deep multi-layer analysis of Alzheimer’s disease brain reveals strong proteomic disease-related changes not observed at the RNA level |
title_short | Large-scale deep multi-layer analysis of Alzheimer’s disease brain reveals strong proteomic disease-related changes not observed at the RNA level |
title_sort | large-scale deep multi-layer analysis of alzheimer’s disease brain reveals strong proteomic disease-related changes not observed at the rna level |
topic | Resource |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8825285/ https://www.ncbi.nlm.nih.gov/pubmed/35115731 http://dx.doi.org/10.1038/s41593-021-00999-y |
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