Differential transcript usage unravels gene expression alterations in Alzheimer’s disease human brains

Coelho, Diego Marques; Iohan, Lukas da Cruz Carvalho; Farias, Ana Raquel Melo de; Flaig, Amandine; Lambert, Jean-Charles; Costa, Marcos Romualdo

Differential transcript usage unravels gene expression alterations in Alzheimer’s disease human brains

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dc.contributor.author	Coelho, Diego Marques
dc.contributor.author	Iohan, Lukas da Cruz Carvalho
dc.contributor.author	Farias, Ana Raquel Melo de
dc.contributor.author	Flaig, Amandine
dc.contributor.author	Lambert, Jean-Charles
dc.contributor.author	Costa, Marcos Romualdo
dc.date.accessioned	2021-01-05T17:23:02Z
dc.date.available	2021-01-05T17:23:02Z
dc.date.issued	2021-01-04
dc.description.resumo	Alzheimer’s disease (AD) is the leading cause of dementia in aging individuals. Yet, the pathophysiological processes involved in AD onset and progression are still poorly understood. Among numerous strategies, a comprehensive overview of gene expression alterations in the diseased brain could contribute for a better understanding of the AD pathology. In this work, we probed the differential expression of genes in different brain regions of healthy and AD adult subjects using data from three large transcriptomic studies: Mayo Clinic, Mount Sinai Brain Bank (MSBB), and ROSMAP. Using a combination of differential expression of gene and isoform switch analyses, we provide a detailed landscape of gene expression alterations in the temporal and frontal lobes, harboring brain areas affected at early and late stages of the AD pathology, respectively. Next, we took advantage of an indirect approach to assign the complex gene expression changes revealed in bulk RNAseq to individual cell types/subtypes of the adult brain. This strategy allowed us to identify previously overlooked gene expression changes in the brain of AD patients. Among these alterations, we show isoform switches in the AD causal gene amyloid-beta precursor protein (APP) and the risk gene bridging integrator 1 (BIN1), which could have important functional consequences in neuronal cells. Altogether, our work proposes a novel integrative strategy to analyze RNAseq data in AD and other neurodegenerative diseases based on both gene/transcript expression and regional/cell-type specificities	pt_BR
dc.identifier.citation	MARQUES-COELHO, Diego; IOHAN, Lukas da Cruz Carvalho; FARIAS, Ana Raquel Melo de; FLAIG, Amandine; LAMBERT, Jean-Charles; COSTA, Marcos Romualdo. Differential transcript usage unravels gene expression alterations in Alzheimer’s disease human brains. Npj Aging And Mechanisms Of Disease, [S. l.], v. 7, n. 1, jan. 2021. doi: http://dx.doi.org/10.1038/s41514-020-00052-5. Disponível em: https://www.nature.com/articles/s41514-020-00052-5#citeas. Acesso em: 05 jan. 2021.	pt_BR
dc.identifier.doi	https://doi.org/10.1038/s41514-020-00052-5
dc.identifier.uri	https://repositorio.ufrn.br/handle/123456789/31194
dc.language	en	pt_BR
dc.publisher	Springer Science and Business Media LLC	pt_BR
dc.rights	Attribution 3.0 Brazil	*
dc.rights.uri	http://creativecommons.org/licenses/by/3.0/br/	*
dc.subject	Alzheimer disease	pt_BR
dc.subject	Gene expression	pt_BR
dc.subject	Temporal lobe	pt_BR
dc.subject	Frontal lobe	pt_BR
dc.subject	Gene expression profiling	pt_BR
dc.title	Differential transcript usage unravels gene expression alterations in Alzheimer’s disease human brains	pt_BR
dc.type	article	pt_BR