dc.contributor.author | Tosh, JL | en_US |
dc.contributor.author | Rhymes, ER | en_US |
dc.contributor.author | Mumford, P | en_US |
dc.contributor.author | Whittaker, HT | en_US |
dc.contributor.author | Pulford, LJ | en_US |
dc.contributor.author | Noy, SJ | en_US |
dc.contributor.author | Cleverley, K | en_US |
dc.contributor.author | LonDownS Consortium | en_US |
dc.contributor.author | Walker, MC | en_US |
dc.contributor.author | Tybulewicz, VLJ | en_US |
dc.contributor.author | Wykes, RC | en_US |
dc.contributor.author | Fisher, EMC | en_US |
dc.contributor.author | Wiseman, FK | en_US |
dc.date.accessioned | 2023-09-14T08:12:56Z | |
dc.date.available | 2021-02-23 | en_US |
dc.date.issued | 2021-03-11 | en_US |
dc.identifier.uri | https://qmro.qmul.ac.uk/xmlui/handle/123456789/90698 | |
dc.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. | en_US |
dc.format.extent | 5736 - ? | en_US |
dc.language | eng | en_US |
dc.relation.ispartof | Sci Rep | en_US |
dc.rights | Attribution 3.0 United States | * |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/us/ | * |
dc.subject | Alzheimer Disease | en_US |
dc.subject | Amyloid beta-Peptides | en_US |
dc.subject | Amyloid beta-Protein Precursor | en_US |
dc.subject | Animals | en_US |
dc.subject | Brain | en_US |
dc.subject | Chromosomes, Mammalian | en_US |
dc.subject | Disease Models, Animal | en_US |
dc.subject | Down Syndrome | en_US |
dc.subject | Mice | en_US |
dc.subject | Mice, Transgenic | en_US |
dc.subject | Phenotype | en_US |
dc.subject | Phosphotransferases | en_US |
dc.subject | Protein Aggregates | en_US |
dc.subject | Protein-Arginine N-Methyltransferases | en_US |
dc.subject | Segmental Duplications, Genomic | en_US |
dc.subject | Seizures | en_US |
dc.subject | Solubility | en_US |
dc.subject | Survival Analysis | en_US |
dc.subject | Transgenes | en_US |
dc.title | Genetic dissection of down syndrome-associated alterations in APP/amyloid-β biology using mouse models. | en_US |
dc.type | Article | |
dc.identifier.doi | 10.1038/s41598-021-85062-3 | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/33707583 | en_US |
pubs.issue | 1 | en_US |
pubs.notes | Not known | en_US |
pubs.publication-status | Published online | en_US |
pubs.volume | 11 | en_US |
dcterms.dateAccepted | 2021-02-23 | en_US |