1. Universidade Federal do Rio Grande do Norte
2. Instituto do Cérebro
3. ICe - Artigos publicados em periódicos

Título:	Analysis of modular gene co-expression networks reveals molecular pathways underlying Alzheimer’s disease and progressive supranuclear palsy
Autor(es):	Iohan, Lukas da Cruz Carvalho Lambert, Jean-Charles Costa, Marcos Romualdo
Palavras-chave:	Alzheimer disease;Supranuclear palsy, progressive;Neurodegenerative diseases;Models, animal;Tauopathies;Amyloidopathy
Data do documento:	14-Abr-2022
Editor:	Public Library of Science (PLoS)
Referência:	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. Plos One, [S. l.], v. 17, n. 4, p. e0266405-2, abr. 2022. Doi: http://dx.doi.org/10.1371/journal.pone.0266405. Disponível em: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0266405. Acesso em: 18 abr. 2022.
Resumo:	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
URI:	https://repositorio.ufrn.br/handle/123456789/46968
Aparece nas coleções:	ICe - Artigos publicados em periódicos

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