Your browser doesn't support javascript.
loading
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.
Afiliação
  • Iohan LDCC; Brain Institute, Federal University of Rio Grande do Norte, Natal, Brazil.
  • Lambert JC; Bioinformatics Multidisciplinary Environment, Federal University of Rio Grande do Norte, Natal, Brazil.
  • Costa MR; Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1167-RID-AGE Facteurs de Risque et Déterminants Moléculaires des Maladies Liées au Vieillissement, DISTALZ, Lille, France.
PLoS One ; 17(4): e0266405, 2022.
Article em En | MEDLINE | ID: mdl-35421130
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Paralisia Supranuclear Progressiva / Tauopatias / Doença de Alzheimer Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Aged / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Paralisia Supranuclear Progressiva / Tauopatias / Doença de Alzheimer Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Aged / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article