Summary
The intent of this proposal is to improve our understanding of how an extra chromosome 21 affects cellular processes that result in cognitive deficits and increased risks for other conditions in Down syndrome, particularly early-onset Alzheimer’s disease (AD). Using a novel method of “trisomy silencing” (correction) to inactivate one chromosome 21 in DS stem cells, we will test central concepts, question some existing assumptions, and identify differences in cell state or development to inform therapeutic strategies. Our studies will improve understanding of how and when trisomy impacts brain and vascular systems, and when effects may be reversible. Additionally, a breakthrough approach will be tested in relation to AD and autism.