Article ; Online: Genetic dissection of down syndrome-associated alterations in APP/amyloid-β biology using mouse models.
2021 Volume 11, Issue 1, Page(s) 5736
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 ...
| 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. |
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| MeSH term(s) | Alzheimer Disease/complications ; Alzheimer Disease/genetics ; Amyloid beta-Peptides/chemistry ; Amyloid beta-Peptides/genetics ; Amyloid beta-Protein Precursor/genetics ; Animals ; Brain/pathology ; Chromosomes, Mammalian/genetics ; Disease Models, Animal ; Down Syndrome/complications ; Down Syndrome/genetics ; Mice ; Mice, Transgenic ; Phenotype ; Phosphotransferases/metabolism ; Protein Aggregates ; Protein-Arginine N-Methyltransferases/metabolism ; Segmental Duplications, Genomic ; Seizures/complications ; Seizures/pathology ; Solubility ; Survival Analysis ; Transgenes |
| Chemical Substances | Amyloid beta-Peptides ; Amyloid beta-Protein Precursor ; Protein Aggregates ; PRMT2 protein, mouse (EC 2.1.1.319) ; Protein-Arginine N-Methyltransferases (EC 2.1.1.319) ; Pdxk protein, mouse (EC 2.7.-) ; Phosphotransferases (EC 2.7.-) |
| Language | English |
| Publishing date | 2021-03-11 |
| Publishing country | England |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2615211-3 |
| ISSN | 2045-2322 ; 2045-2322 |
| ISSN (online) | 2045-2322 |
| ISSN | 2045-2322 |
| DOI | 10.1038/s41598-021-85062-3 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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