Genetic dissection of down syndrome-associated alterations in APP/amyloid-β biology using mouse models

Abstract Individuals who have Down syndrome (caused by trisomy of chromosome 21), have a greatly elevated risk of early-onset Alzheimer’s disease, in which amyloid-β accumulates in the brain. Amyloid-β is a product of the chromosome 21 gene APP (amyloid precursor protein) and the extra copy or ‘dose...

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Autores principales:	Justin L. Tosh, Elena R. Rhymes, Paige Mumford, Heather T. Whittaker, Laura J. Pulford, Sue J. Noy, Karen Cleverley, LonDownS Consortium, Matthew C. Walker, Victor L. J. Tybulewicz, Rob C. Wykes, Elizabeth M. C. Fisher, Frances K. Wiseman
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/976af835ad394de686b40b465f483f68
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spelling	oai:doaj.org-article:976af835ad394de686b40b465f483f682021-12-02T15:54:01ZGenetic dissection of down syndrome-associated alterations in APP/amyloid-β biology using mouse models10.1038/s41598-021-85062-32045-2322https://doaj.org/article/976af835ad394de686b40b465f483f682021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85062-3https://doaj.org/toc/2045-2322Abstract Individuals who have Down syndrome (caused by trisomy of chromosome 21), have a greatly elevated risk of early-onset Alzheimer’s disease, in which amyloid-β accumulates in the brain. Amyloid-β is a product of the chromosome 21 gene APP (amyloid precursor protein) and the extra copy or ‘dose’ of APP is thought to be the cause of this early-onset Alzheimer’s disease. However, other chromosome 21 genes likely modulate disease when in three-copies in people with Down syndrome. Here we show that an extra copy of chromosome 21 genes, other than APP, influences APP/Aβ biology. We crossed Down syndrome mouse models with partial trisomies, to an APP transgenic model and found that extra copies of subgroups of chromosome 21 gene(s) modulate amyloid-β aggregation and APP transgene-associated mortality, independently of changing amyloid precursor protein abundance. Thus, genes on chromosome 21, other than APP, likely modulate Alzheimer’s disease in people who have Down syndrome.Justin L. ToshElena R. RhymesPaige MumfordHeather T. WhittakerLaura J. PulfordSue J. NoyKaren CleverleyLonDownS ConsortiumMatthew C. WalkerVictor L. J. TybulewiczRob C. WykesElizabeth M. C. FisherFrances K. WisemanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Justin L. Tosh Elena R. Rhymes Paige Mumford Heather T. Whittaker Laura J. Pulford Sue J. Noy Karen Cleverley LonDownS Consortium Matthew C. Walker Victor L. J. Tybulewicz Rob C. Wykes Elizabeth M. C. Fisher Frances K. Wiseman Genetic dissection of down syndrome-associated alterations in APP/amyloid-β biology using mouse models
description	Abstract Individuals who have Down syndrome (caused by trisomy of chromosome 21), have a greatly elevated risk of early-onset Alzheimer’s disease, in which amyloid-β accumulates in the brain. Amyloid-β is a product of the chromosome 21 gene APP (amyloid precursor protein) and the extra copy or ‘dose’ of APP is thought to be the cause of this early-onset Alzheimer’s disease. However, other chromosome 21 genes likely modulate disease when in three-copies in people with Down syndrome. Here we show that an extra copy of chromosome 21 genes, other than APP, influences APP/Aβ biology. We crossed Down syndrome mouse models with partial trisomies, to an APP transgenic model and found that extra copies of subgroups of chromosome 21 gene(s) modulate amyloid-β aggregation and APP transgene-associated mortality, independently of changing amyloid precursor protein abundance. Thus, genes on chromosome 21, other than APP, likely modulate Alzheimer’s disease in people who have Down syndrome.
format	article
author	Justin L. Tosh Elena R. Rhymes Paige Mumford Heather T. Whittaker Laura J. Pulford Sue J. Noy Karen Cleverley LonDownS Consortium Matthew C. Walker Victor L. J. Tybulewicz Rob C. Wykes Elizabeth M. C. Fisher Frances K. Wiseman
author_facet	Justin L. Tosh Elena R. Rhymes Paige Mumford Heather T. Whittaker Laura J. Pulford Sue J. Noy Karen Cleverley LonDownS Consortium Matthew C. Walker Victor L. J. Tybulewicz Rob C. Wykes Elizabeth M. C. Fisher Frances K. Wiseman
author_sort	Justin L. Tosh
title	Genetic dissection of down syndrome-associated alterations in APP/amyloid-β biology using mouse models
title_short	Genetic dissection of down syndrome-associated alterations in APP/amyloid-β biology using mouse models
title_full	Genetic dissection of down syndrome-associated alterations in APP/amyloid-β biology using mouse models
title_fullStr	Genetic dissection of down syndrome-associated alterations in APP/amyloid-β biology using mouse models
title_full_unstemmed	Genetic dissection of down syndrome-associated alterations in APP/amyloid-β biology using mouse models
title_sort	genetic dissection of down syndrome-associated alterations in app/amyloid-β biology using mouse models
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/976af835ad394de686b40b465f483f68
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Genetic dissection of down syndrome-associated alterations in APP/amyloid-β biology using mouse models

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