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

Abstract 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 co...

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Autores principales:	Diego Marques-Coelho, Lukas da Cruz Carvalho Iohan, Ana Raquel Melo de Farias, Amandine Flaig, The Brainbank Neuro–CEB Neuropathology Network, Jean-Charles Lambert, Marcos Romualdo Costa
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Geriatrics RC952-954.6
Acceso en línea:	https://doaj.org/article/d9b5cd0c8e78499db37977012745cbe4
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spelling	oai:doaj.org-article:d9b5cd0c8e78499db37977012745cbe42021-12-02T14:23:46ZDifferential transcript usage unravels gene expression alterations in Alzheimer’s disease human brains10.1038/s41514-020-00052-52056-3973https://doaj.org/article/d9b5cd0c8e78499db37977012745cbe42021-01-01T00:00:00Zhttps://doi.org/10.1038/s41514-020-00052-5https://doaj.org/toc/2056-3973Abstract 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.Diego Marques-CoelhoLukas da Cruz Carvalho IohanAna Raquel Melo de FariasAmandine FlaigThe Brainbank Neuro–CEB Neuropathology NetworkJean-Charles LambertMarcos Romualdo CostaNature PortfolioarticleGeriatricsRC952-954.6ENnpj Aging and Mechanisms of Disease, Vol 7, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Geriatrics RC952-954.6
spellingShingle	Geriatrics RC952-954.6 Diego Marques-Coelho Lukas da Cruz Carvalho Iohan Ana Raquel Melo de Farias Amandine Flaig The Brainbank Neuro–CEB Neuropathology Network Jean-Charles Lambert Marcos Romualdo Costa Differential transcript usage unravels gene expression alterations in Alzheimer’s disease human brains
description	Abstract 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.
format	article
author	Diego Marques-Coelho Lukas da Cruz Carvalho Iohan Ana Raquel Melo de Farias Amandine Flaig The Brainbank Neuro–CEB Neuropathology Network Jean-Charles Lambert Marcos Romualdo Costa
author_facet	Diego Marques-Coelho Lukas da Cruz Carvalho Iohan Ana Raquel Melo de Farias Amandine Flaig The Brainbank Neuro–CEB Neuropathology Network Jean-Charles Lambert Marcos Romualdo Costa
author_sort	Diego Marques-Coelho
title	Differential transcript usage unravels gene expression alterations in Alzheimer’s disease human brains
title_short	Differential transcript usage unravels gene expression alterations in Alzheimer’s disease human brains
title_full	Differential transcript usage unravels gene expression alterations in Alzheimer’s disease human brains
title_fullStr	Differential transcript usage unravels gene expression alterations in Alzheimer’s disease human brains
title_full_unstemmed	Differential transcript usage unravels gene expression alterations in Alzheimer’s disease human brains
title_sort	differential transcript usage unravels gene expression alterations in alzheimer’s disease human brains
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/d9b5cd0c8e78499db37977012745cbe4
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Differential transcript usage unravels gene expression alterations in Alzheimer’s disease human brains

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