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Analysis of modular gene co-expression networks reveals molecular pathways underlying Alzheimer’s disease and progressive supranuclear palsy

A comprehensive understanding of the pathological mechanisms involved at different stages of neurodegenerative diseases is key for the advance of preventive and disease-modifying treatments. Gene expression alterations in the diseased brain is a potential source of information about biological proce...

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Autores principales: Iohan, Lukas da Cruz Carvalho, Lambert, Jean-Charles, Costa, Marcos R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9009680/
https://www.ncbi.nlm.nih.gov/pubmed/35421130
http://dx.doi.org/10.1371/journal.pone.0266405
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author Iohan, Lukas da Cruz Carvalho
Lambert, Jean-Charles
Costa, Marcos R.
author_facet Iohan, Lukas da Cruz Carvalho
Lambert, Jean-Charles
Costa, Marcos R.
author_sort Iohan, Lukas da Cruz Carvalho
collection PubMed
description A comprehensive understanding of the pathological mechanisms involved at different stages of neurodegenerative diseases is key for the advance of preventive and disease-modifying treatments. Gene expression alterations in the diseased brain is a potential source of information about biological processes affected by pathology. In this work, we performed a systematic comparison of gene expression alterations in the brains of human patients diagnosed with Alzheimer’s disease (AD) or Progressive Supranuclear Palsy (PSP) and animal models of amyloidopathy and tauopathy. Using a systems biology approach to uncover biological processes associated with gene expression alterations, we could pinpoint processes more strongly associated with tauopathy/PSP and amyloidopathy/AD. We show that gene expression alterations related to immune-inflammatory responses preponderate in younger, whereas those associated to synaptic transmission are mainly observed in older AD patients. In PSP, however, changes associated with immune-inflammatory responses and synaptic transmission overlap. These two different patterns observed in AD and PSP brains are fairly recapitulated in animal models of amyloidopathy and tauopathy, respectively. Moreover, in AD, but not PSP or animal models, gene expression alterations related to RNA splicing are highly prevalent, whereas those associated with myelination are enriched both in AD and PSP, but not in animal models. Finally, we identify 12 AD and 4 PSP genetic risk factors in cell-type specific co-expression modules, thus contributing to unveil the possible role of these genes to pathogenesis. Altogether, this work contributes to unravel the potential biological processes affected by amyloid versus tau pathology and how they could contribute to the pathogenesis of AD and PSP.
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spelling pubmed-90096802022-04-15 Analysis of modular gene co-expression networks reveals molecular pathways underlying Alzheimer’s disease and progressive supranuclear palsy Iohan, Lukas da Cruz Carvalho Lambert, Jean-Charles Costa, Marcos R. PLoS One Research Article A comprehensive understanding of the pathological mechanisms involved at different stages of neurodegenerative diseases is key for the advance of preventive and disease-modifying treatments. Gene expression alterations in the diseased brain is a potential source of information about biological processes affected by pathology. In this work, we performed a systematic comparison of gene expression alterations in the brains of human patients diagnosed with Alzheimer’s disease (AD) or Progressive Supranuclear Palsy (PSP) and animal models of amyloidopathy and tauopathy. Using a systems biology approach to uncover biological processes associated with gene expression alterations, we could pinpoint processes more strongly associated with tauopathy/PSP and amyloidopathy/AD. We show that gene expression alterations related to immune-inflammatory responses preponderate in younger, whereas those associated to synaptic transmission are mainly observed in older AD patients. In PSP, however, changes associated with immune-inflammatory responses and synaptic transmission overlap. These two different patterns observed in AD and PSP brains are fairly recapitulated in animal models of amyloidopathy and tauopathy, respectively. Moreover, in AD, but not PSP or animal models, gene expression alterations related to RNA splicing are highly prevalent, whereas those associated with myelination are enriched both in AD and PSP, but not in animal models. Finally, we identify 12 AD and 4 PSP genetic risk factors in cell-type specific co-expression modules, thus contributing to unveil the possible role of these genes to pathogenesis. Altogether, this work contributes to unravel the potential biological processes affected by amyloid versus tau pathology and how they could contribute to the pathogenesis of AD and PSP. Public Library of Science 2022-04-14 /pmc/articles/PMC9009680/ /pubmed/35421130 http://dx.doi.org/10.1371/journal.pone.0266405 Text en © 2022 Iohan et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Iohan, Lukas da Cruz Carvalho
Lambert, Jean-Charles
Costa, Marcos R.
Analysis of modular gene co-expression networks reveals molecular pathways underlying Alzheimer’s disease and progressive supranuclear palsy
title Analysis of modular gene co-expression networks reveals molecular pathways underlying Alzheimer’s disease and progressive supranuclear palsy
title_full Analysis of modular gene co-expression networks reveals molecular pathways underlying Alzheimer’s disease and progressive supranuclear palsy
title_fullStr Analysis of modular gene co-expression networks reveals molecular pathways underlying Alzheimer’s disease and progressive supranuclear palsy
title_full_unstemmed Analysis of modular gene co-expression networks reveals molecular pathways underlying Alzheimer’s disease and progressive supranuclear palsy
title_short Analysis of modular gene co-expression networks reveals molecular pathways underlying Alzheimer’s disease and progressive supranuclear palsy
title_sort analysis of modular gene co-expression networks reveals molecular pathways underlying alzheimer’s disease and progressive supranuclear palsy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9009680/
https://www.ncbi.nlm.nih.gov/pubmed/35421130
http://dx.doi.org/10.1371/journal.pone.0266405
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