| First Author | Tosh JL | Year | 2021 |
| Journal | Sci Rep | Volume | 11 |
| Issue | 1 | Pages | 5736 |
| PubMed ID | 33707583 | Mgi Jnum | J:304829 |
| Mgi Id | MGI:6695510 | Doi | 10.1038/s41598-021-85062-3 |
| Citation | Tosh JL, et al. (2021) Genetic dissection of down syndrome-associated alterations in APP/amyloid-beta biology using mouse models. Sci Rep 11(1):5736 |
| abstractText | 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-beta accumulates in the brain. Amyloid-beta 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/Abeta 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-beta 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. |
