Reports of a successful vaccine against Alzheimer's disease are causing excitement in the scientific community. The vaccine induces an immune response specifically against beta-amyloid (the protein that makes up senile plaques in Alzheimer's) and has been shown to reduce and prevent plaque formation in mice. Scientists have now shown that vaccination with this peptide is also associated with an improvement in cognitive function (Nature 2000;408:979-84).
Although a number of pathophysiological changes occur in the brains of people who develop Alzheimer's disease, beta-amyloid and its precursor protein are known to have a central role in how the disease comes about. About a year ago, Elan Pharmaceuticals reported immunisation of a transgenic mouse model with the beta-amyloid peptide. The mouse model was genetically engineered to mimic Alzheimer's, and after immunisation it was shown that the number of beta-amyloid plaques in the brains of these animals was significantly reduced. The researchers did not at that time look for any effects on cognition.
Mice are considered a good animal model for Alzheimer's disease, and as there are no primate models the next step would be to test any vaccine in humans. Now, as reported in Nature, two separate research teams have replicated and extended these results, showing that vaccination was also accompanied by a corresponding improvement in cognitive and memory functions. The cognitive skills of the mice were tested using a water maze. The level of cognitive function required to master the maze roughly equates with the sort of cognitive and memory skills needed by human beings trying to find their way from one location to another (from home to the shops and back, for example). Such deficits are commonly encountered in patients with Alzheimer's when they start wandering.
Professor Peter St George-Hyslop, professor of medicine and neurology, and his team at the University of Toronto, authors of one of the papers, immunised about 30 normal and 30 transgenic mice with either beta-amyloid peptide or placebo protein. The normal mice displayed no changes after immunisation with either protein. The transgenic mice immunised with placebo gave a progressively poorer performance in the water maze and had increasing deposits of beta-amyloid peptide in senile plaques. In contrast, transgenic mice immunised with beta-amyloid peptide achieved a good performance, which was about 75% of that achieved by the healthy mice. These changes in function were detectable four weeks after immunisation and lasted at least four months. Improvement in function was accompanied by a 50% reduct-ion in plaque formation.
What does it mean for humans?
This sort of vaccine may turn out to be useful in prevention rather than treatment of established disease, and this in turn leads to the need to find a reliable and subtle preclinical diagnostic test for Alzheimer's disease. “I'm cautiously optimistic,” says Professor St George-Hyslop. Harry Cayton, chief executive of the Alzheimer's Society, believes these results are “very significant.” He says that the society's “normally reserved scientific advisers are very excited.” Although Alzheimer's disease is known not to have a single cause, and it is not yet clear whether removing senile plaques is sufficient to have an important effect on humans. Mr Cayton says “this vaccine goes beyond the present drug treatments and may kickstart research in a whole new direction.”
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ULRIKE PREUSS
Doctors Juliet Nelson, Peter Hambly (right, front) and Bob Baker (right, back) entertaining guests at the BMJ”s first Christmas Revue at Wilton”s Music Hall, east London, on 12 December.