Differential transcript usage unravels gene expression alterations in Alzheimer's disease human brains.
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 contr...
| Publicado en: | NPJ Aging & Mechanisms of Disease Vol. 7; no. 1; pp. 1 - 16 |
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| Autores principales: | , , , , , , , , , , , , , , , , , , , |
| Formato: | Journal Article |
| Publicado: |
Springer Nature
1/4/2021
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=147907977&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 147907977 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 20563973 KIPB jtl: NPJ Aging & Mechanisms of Disease issn: 20563973 maglogo: N pubinfo: dt: 1/4/2021 vid: 7 iid: 1 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 147907977 10.1038/s41514-020-00052-5 147907977 ppf: 1 ppct: 15 formats: tig: atl: Differential transcript usage unravels gene expression alterations in Alzheimer's disease human brains. aug: au: Marques-Coelho, Diego Iohan, Lukas da Cruz Carvalho Melo de Farias, Ana Raquel Flaig, Amandine Letournel, Franck Martin-Négrier, Marie-Laure Chapon, Françoise Faisant, Maxime Godfraind, Catherine Maurage, Claude-Alain Deramecourt, Vincent Duchesne, Mathilde Meyronnet, David Streichenberger, Nathalie de Paula, André Mauès Rigau, Valérie Vandenbos-Burel, Fanny Duyckaerts, Charles Seilhean, Danielle Milin, Serge affil: Brain Institute, Federal University of Rio Grande do Norte, Av. Nascimento de Castro, 2155, Natal, Brazil sug: ab: 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. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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