Scientists have fingered a new suspect in the brain cell deaths that underlie Alzheimer's disease. According to test-tube findings reported in today's issue of Biochemistry, protein plaques that riddle victims' brains appear to produce hydrogen peroxide, or bleach, which is toxic to nerve cells. Shutting off this reaction may be a way to slow the progressive disorder, which is the fourth leading cause of death in Western countries.
Ever since the days of Alois Alzheimer, neuroscientists have known that a protein called amyloid globs together in plaques in the brains of Alzheimer's patients. But debate still rages over whether the plaques themselves kill brain cells, the loss of which leads to dementia.
A few years ago researchers began to find hydrogen peroxide (H2O2), a corrosive compound that can kill neurons, in patients' brains; how it got there was a mystery. Most scientists assumed it was produced by some reaction in the dying cells. Ashley Bush, a psychiatrist at Harvard Medical School in Boston, and colleagues wondered whether the hydrogen peroxide might come from the plaques themselves. In test tubes, the researchers mixed solutions of amyloid protein with solutions of copper and iron ions, which are plentiful in the brain. They discovered that the amyloid protein bound the metal ions and gave off hydrogen peroxide as a byproduct. The researchers also showed that chelators--chemicals that capture metals--are capable of shutting down hydrogen peroxide production almost completely.
The findings are the first evidence "that plaques can generate a neuron-killing chemical," says Vassilis Koliatsos, a neuropathologist at The Johns Hopkins University School of Medicine. Bush's team next plans to see whether the plaques pump out H202 in the body. If so, he says, chelating compounds that specifically tie up copper and iron could be tested as potential Alzheimer's drugs.