A CURE for Alzheimer鈥檚 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鈥檚 Nature (vol 400, p 173). They
hope to begin tests this year in people with the disease.
As Alzheimer鈥檚 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鈥檚 disease, the
protein is two amino acids longer than normal. It is insoluble and so forms
whitish plaques in the brain.
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Many researchers believe these plaques cause the symptoms of Alzheimer鈥檚. But
others blame a second change: the formation of tangles of a protein called tau
inside sufferers鈥� 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鈥檚 disease (In Brief, 11
February 1995, p 11). The mice develop plaques of amyloid-beta like those in
people with Alzheimer鈥檚.
Now the Athena team has shown that injecting these mice with small quantities
of insoluble amyloid-beta can prevent the plaques building up. 鈥淚f you start
immunising when the animals are young, they never develop plaques,鈥� 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鈥檛 normally react against amyloid-beta. But Schenk鈥檚
team combined it with Freund鈥檚 adjuvant鈥攁 crude mix of oil, water and dead
bacteria鈥攚hich fired up the immune system so that it attacked the
protein.
The inoculations also shrank existing plaques in adult mice to almost
nothing鈥攚hich leads Schenk to believe the injections could cure patients
who are starting to show symptoms. Athena鈥檚 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鈥檚, those hopes
will be dashed. 鈥淭he pessimist will say you鈥檙e just going to get a clean brain,
but it鈥檚 not going to alter the symptoms,鈥� 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鈥檛 seem to lose their faculties. And while their brain
cells shrivel, they don鈥檛 actually die.
Schenk argues that mice will never show the same symptoms as people because
their brains don鈥檛 have to do things like plan meals or decide what to
wear鈥攖he sort of higher cognitive functions that are lost in Alzheimer鈥檚
patients. He also points out that amyloid-beta can kill the brain cells of our
primate relatives.
Alzheimer鈥檚 researchers are now waiting for the results of the planned
clinical trials. 鈥淲e鈥檙e not going to know until more experiments are done,鈥� says
St George-Hyslop.
