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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Clinical Investigation 2022
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.
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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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