Some 300,000 people in the United States have Down syndrome, caused by a third, extra copy of chromosome 21. In addition to being linked to congenital heart disease, hearing deficits and leukemia, Down syndrome is the top cause of mental retardation in this country and often leads to early-onset Alzheimer’s disease. But little research has been done to develop therapies that would arrest or reverse patients’ cognitive decline. Until recently.
Researchers led by neurology professor William Mobley and senior research scientist Ahmad Salehi have identified a possible cause for mental retardation in Down syndrome. Using a mouse model, they discovered that having three copies of a gene called App—for amyloid precursor protein—interferes with a feedback loop for neuronal growth, causing neurons to wither away. App mutations are known to cause early-onset Alzheimer’s in otherwise healthy people.
The Stanford researchers, who reported their findings in the July 6 issue of the journal Neuron, caution that their research is preliminary, and that they have not found the sole cause for cognitive difficulties in people with Down syndrome.
Nevertheless, they are hopeful they have taken the first step toward a significant treatment. “First, we need to figure out at a molecular level how App works in Down syndrome,” says Mobley, PhD ’74, MD ’76. “Then we need to examine other genes that might be involved and test possible compounds in mouse and human cells. If we are able to do all that, we might begin to think of helping children and adults with Down syndrome to develop and age more normally.”
