Discovery of gene mutation gives hope for Down syndrome and Alzheimer's victims

Jul 6 2006

Researchers in the U.S. have discovered a gene mutation that shrivels brain cells which they suspect is responsible for the mental retardation seen in Down syndrome.

The believe the discovery may offer ways to interfere with or even reverse the mental deterioration often seen as people with Down syndrome get older and may also be applicable to patients with Alzheimer's disease.

Dr. William Mobley, a neurologist with the Stanford University School of Medicine and Lucile Packard Children's Hospital in California, the senior author of the research, says the reducing the expression of the gene turns down its activity.

Down syndrome is the most frequent genetic cause of mental retardation and affects one out of 800 babies born and is caused when people have an extra copy of chromosome 21, making three instead of two.

The syndrome causes early learning difficulties and sometimes childhood heart disease and leukemia and the majority of people born with Down syndrome will develop Alzheimer's disease by the age of 40.

The researchers used genetically engineered mice to pin down the gene, which is called App (amyloid precursor protein), mutations of which are known to cause early-onset Alzheimer's disease in otherwise healthy people.

The mice had three abnormal copies of the App gene and the researchers found that when the third copy of App was deleted the mice became more normal.

Dr. Ahmad Salehi, who led the study, says they are now investigating ways of reducing the App expression by one-third, from 150 percent of normal back down to 100 percent.

Although mutations in the gene can cause early-onset Alzheimer's disease in otherwise healthy people, this is the first time it has been linked directly to degeneration of a specific group of neurons in the brains of those with Down syndrome.

The breakthrough confirms an idea suggested by previous research that the mental deterioration in people with Down syndrome is the result of an interrupted conversation between nerve cells in a specific part of the brain.

The researchers say the findings are tantalizing, but many steps remain before an effective therapy is available for the devastating disorders.

The fact that deleting the third copy of App did not restore the mouse to normal indicates that other genes must also affect the timing or severity of the mental degeneration.

The research is published in the July 6 issue of Neuron.