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Alzheimer’s disease and progressive supranuclear palsy share similar transcriptomic changes in distinct brain regions
Vast numbers of differentially expressed genes and perturbed networks have been identified in Alzheimer’s disease (AD), however, neither disease nor brain region specificity of these transcriptome alterations has been explored. Using RNA-Seq data from 231 temporal cortex and 224 cerebellum samples f...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Clinical Investigation
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8759790/ https://www.ncbi.nlm.nih.gov/pubmed/34813500 http://dx.doi.org/10.1172/JCI149904 |
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author | Wang, Xue Allen, Mariet İş, Özkan Reddy, Joseph S. Tutor-New, Frederick Q. Castanedes Casey, Monica Carrasquillo, Minerva M. Oatman, Stephanie R. Min, Yuhao Asmann, Yan W. Funk, Cory Nguyen, Thuy Ho, Charlotte C.G. Malphrus, Kimberly G. Seyfried, Nicholas T. Levey, Allan I. Younkin, Steven G. Murray, Melissa E. Dickson, Dennis W. Price, Nathan D. Golde, Todd E. Ertekin-Taner, Nilüfer |
author_facet | Wang, Xue Allen, Mariet İş, Özkan Reddy, Joseph S. Tutor-New, Frederick Q. Castanedes Casey, Monica Carrasquillo, Minerva M. Oatman, Stephanie R. Min, Yuhao Asmann, Yan W. Funk, Cory Nguyen, Thuy Ho, Charlotte C.G. Malphrus, Kimberly G. Seyfried, Nicholas T. Levey, Allan I. Younkin, Steven G. Murray, Melissa E. Dickson, Dennis W. Price, Nathan D. Golde, Todd E. Ertekin-Taner, Nilüfer |
author_sort | Wang, Xue |
collection | PubMed |
description | Vast numbers of differentially expressed genes and perturbed networks have been identified in Alzheimer’s disease (AD), however, neither disease nor brain region specificity of these transcriptome alterations has been explored. Using RNA-Seq data from 231 temporal cortex and 224 cerebellum samples from patients with AD and progressive supranuclear palsy (PSP), a tauopathy, we identified a striking correlation in the directionality and magnitude of gene expression changes between these 2 neurodegenerative proteinopathies. Further, the transcriptomic changes in AD and PSP brains ware highly conserved between the temporal and cerebellar cortices, indicating that highly similar transcriptional changes occur in pathologically affected and grossly less affected, albeit functionally connected, areas of the brain. Shared up- or downregulated genes in AD and PSP are enriched in biological pathways. Many of these genes also have concordant protein changes and evidence of epigenetic control. These conserved transcriptomic alterations of 2 distinct proteinopathies in brain regions with and without significant gross neuropathology have broad implications. AD and other neurodegenerative diseases are likely characterized by common disease or compensatory pathways with widespread perturbations in the whole brain. These findings can be leveraged to develop multifaceted therapies and biomarkers that address these common, complex, and ubiquitous molecular alterations in neurodegenerative diseases. |
format | Online Article Text |
id | pubmed-8759790 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Society for Clinical Investigation |
record_format | MEDLINE/PubMed |
spelling | pubmed-87597902022-01-19 Alzheimer’s disease and progressive supranuclear palsy share similar transcriptomic changes in distinct brain regions Wang, Xue Allen, Mariet İş, Özkan Reddy, Joseph S. Tutor-New, Frederick Q. Castanedes Casey, Monica Carrasquillo, Minerva M. Oatman, Stephanie R. Min, Yuhao Asmann, Yan W. Funk, Cory Nguyen, Thuy Ho, Charlotte C.G. Malphrus, Kimberly G. Seyfried, Nicholas T. Levey, Allan I. Younkin, Steven G. Murray, Melissa E. Dickson, Dennis W. Price, Nathan D. Golde, Todd E. Ertekin-Taner, Nilüfer J Clin Invest Concise Communication Vast numbers of differentially expressed genes and perturbed networks have been identified in Alzheimer’s disease (AD), however, neither disease nor brain region specificity of these transcriptome alterations has been explored. Using RNA-Seq data from 231 temporal cortex and 224 cerebellum samples from patients with AD and progressive supranuclear palsy (PSP), a tauopathy, we identified a striking correlation in the directionality and magnitude of gene expression changes between these 2 neurodegenerative proteinopathies. Further, the transcriptomic changes in AD and PSP brains ware highly conserved between the temporal and cerebellar cortices, indicating that highly similar transcriptional changes occur in pathologically affected and grossly less affected, albeit functionally connected, areas of the brain. Shared up- or downregulated genes in AD and PSP are enriched in biological pathways. Many of these genes also have concordant protein changes and evidence of epigenetic control. These conserved transcriptomic alterations of 2 distinct proteinopathies in brain regions with and without significant gross neuropathology have broad implications. AD and other neurodegenerative diseases are likely characterized by common disease or compensatory pathways with widespread perturbations in the whole brain. These findings can be leveraged to develop multifaceted therapies and biomarkers that address these common, complex, and ubiquitous molecular alterations in neurodegenerative diseases. American Society for Clinical Investigation 2022-01-18 2022-01-18 /pmc/articles/PMC8759790/ /pubmed/34813500 http://dx.doi.org/10.1172/JCI149904 Text en © 2022 Wang et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Concise Communication Wang, Xue Allen, Mariet İş, Özkan Reddy, Joseph S. Tutor-New, Frederick Q. Castanedes Casey, Monica Carrasquillo, Minerva M. Oatman, Stephanie R. Min, Yuhao Asmann, Yan W. Funk, Cory Nguyen, Thuy Ho, Charlotte C.G. Malphrus, Kimberly G. Seyfried, Nicholas T. Levey, Allan I. Younkin, Steven G. Murray, Melissa E. Dickson, Dennis W. Price, Nathan D. Golde, Todd E. Ertekin-Taner, Nilüfer Alzheimer’s disease and progressive supranuclear palsy share similar transcriptomic changes in distinct brain regions |
title | Alzheimer’s disease and progressive supranuclear palsy share similar transcriptomic changes in distinct brain regions |
title_full | Alzheimer’s disease and progressive supranuclear palsy share similar transcriptomic changes in distinct brain regions |
title_fullStr | Alzheimer’s disease and progressive supranuclear palsy share similar transcriptomic changes in distinct brain regions |
title_full_unstemmed | Alzheimer’s disease and progressive supranuclear palsy share similar transcriptomic changes in distinct brain regions |
title_short | Alzheimer’s disease and progressive supranuclear palsy share similar transcriptomic changes in distinct brain regions |
title_sort | alzheimer’s disease and progressive supranuclear palsy share similar transcriptomic changes in distinct brain regions |
topic | Concise Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8759790/ https://www.ncbi.nlm.nih.gov/pubmed/34813500 http://dx.doi.org/10.1172/JCI149904 |
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