US scientists have discovered that a key gene could trigger the mental impairment and early onset Alzheimer's disease associated with Down syndrome. The findings, reported in two papers published in the journal Neuron, show that the over-production of a gene involved in nerve growth can kill brain cells in mice with symptoms of Down syndrome. The researchers, based at Stanford University and the University of Maryland Baltimore School of Nursing, say their results could eventually lead to ways of stopping or even reversing the mental decline triggered by this process.
Down syndrome - which affects around one in every 750 births - is caused by the presence of three copies of chromosome 21 (the smallest 'bundle' of human genetic material), rather than the usual two. This results in overactivity of the genes located on this chromosome - all of which probably contribute to the features of Down syndrome in some way. In the latest study, the researchers looked at mice bred to have three copies of some of these genes, to try and tease apart their possible effects.
The scientists discovered that in mice with three copies of a gene called amyloid precursor protein (App), the action of a crucial nerve growth factor was disrupted, leading to brain cell death. This did not happen to the same extent in mice that had three copies of most of the other genes involved in Down syndrome, but not App. It was already known that mutations in this gene can cause hereditary Alzheimer's disease - now it seems that an extra copy could also be responsible for dementia in people with Down syndrome.
The team hope that by finding ways to 'damp down' the activity of the App gene's counterpart in humans, it might be possible to curb its harmful effects in people with Down syndrome. However, they stress that other genes must also be involved in the brain decline seen in the condition, since deleting the third copy of App did not restore the mice to normal. But if these other genes can be identified, says Stanford University team leader William Mobley, then 'we might begin to think of helping children and adults with Down syndrome to develop and age more normally'.
Professor Elizabeth Fisher, of University College London, called the work 'very interesting'. She told BBC News Online that 'this may be some way towards an explanation of why people with Down syndrome develop the hallmark brain signs of Alzheimer's disease'.