A Possible Cure For Alzheimer's?
By Jonathan Knight
A cure for Alzheimer's might be within the grasp of researchers at a Californian company. Their unusual vaccine prevents a waste protein building up in the brains of mice. Whether it will help people depends on which of two theories of what causes the disease is correct.
Dale Schenk and his colleagues at Athena Neurosciences in South San Francisco describe their vaccine in this week's Nature (vol 400, p 173). They hope to begin tests this year in people with the disease.
As Alzheimer's sufferers lose memory and judgment, a protein called amyloid-beta builds up in the spaces between their brain cells. Amyloid-beta is a breakdown product of a larger protein, called APP. Usually, amyloid-beta is quickly removed from the body. But in people with Alzheimer's disease, the protein is two amino acids longer than normal. It is insoluble and so forms whitish plaques in the brain.
Many researchers believe these plaques cause the symptoms of Alzheimer's. But others blame a second change: the formation of tangles of a protein called tau inside sufferers' brain cells.
Schenk belongs to the amyloid camp. In 1995, his team bred mice with the human gene that causes an inherited form of Alzheimer's disease (In Brief, 11 February 1995, p 11). The mice develop plaques of amyloid-beta like those in people with Alzheimer's.
Now the Athena team has shown that injecting these mice with small quantities of insoluble amyloid-beta can prevent the plaques building up. "If you start immunising when the animals are young, they never develop plaques," says Schenk.
Schenk and his colleagues injected nine mice with laboratory-made amyloid-beta once a month for 11 months. Two months later, seven of the mice had completely healthy brains and the other two had only a few plaques. By comparison, mice injected with salt solution or with another protein had extensive plaques of amyloid-beta and many shrivelled brain cells.
The immune system doesn't normally react against amyloid-beta. But Schenk's team combined it with Freund's adjuvant--a crude mix of oil, water and dead bacteria--which fired up the immune system so that it attacked the protein.
The inoculations also shrank existing plaques in adult mice to almost nothing--which leads Schenk to believe the injections could cure patients who are starting to show symptoms. Athena's parent company, Elan of Dublin, is applying to the US Food and Drug Administration for permission to give patients injections of amyloid-beta with a more sophisticated immune-stimulating adjuvant.
However, if amyloid plaques are just a by-product of Alzheimer's, those hopes will be dashed. "The pessimist will say you're just going to get a clean brain, but it's not going to alter the symptoms," says Peter St George-Hyslop of the University of Toronto. One reason to be sceptical is that mice bred to have plaque-filled brains don't seem to lose their faculties. And while their brain cells shrivel, they don't actually die.
Schenk argues that mice will never show the same symptoms as people because their brains don't have to do things like plan meals or decide what to wear--the sort of higher cognitive functions that are lost in Alzheimer's patients. He also points out that amyloid-beta can kill the brain cells of our primate relatives.
Alzheimer's researchers are now waiting for the results of the planned clinical trials. "We're not going to know until more experiments are done," says St George-Hyslop.