Genetic dissection of down syndrome-associated alterations in APP/amyloid-β biology using mouse modelsMore about Open Access at the Crick
Authors listJustin L Tosh Elena R Rhymes Paige Mumford Heather T Whittaker Laura J Pulford Sue J Noy Karen Cleverley LonDownS Consortium Matthew C Walker Victor LJ Tybulewicz Rob C Wykes Elizabeth MC Fisher Frances K Wiseman
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.
Journal Scientific Reports
Issue number 1