Published online 21 December 2000 | Nature | doi:10.1038/news001221-10

News

Encouraging results for Alzheimer's vaccine

Vaccinated mice keep their memory in the face of Alzheimer's disease.

Researchers developing a vaccine against Alzheimer's disease have shown that it seems to stop mice with the condition losing their memory1br>. The results boost hopes that such vaccines could delay or prevent similar symptoms in people.

"This is big news," says Paul Chapman who studies Alzheimer's at Cardiff University, UK. "If the results had gone the other way then a lot of people would have been forced to rethink."

The vaccine also reduces the build-up of protein deposits in mouse brains -- the other major indicator of Alzheimer's disease. The pharmaceutical company Elan, based in Dublin, Ireland, is poised to begin large-scale human clinical trials of a potential treatment based on the vaccine. But what works in mice does not always work in people and the vaccine will still have to prove its worth in a battery of further tests.

Nearly one in ten people over the age of 65 suffers the dementia brought on by Alzheimer's disease, and the risk rises fourfold for those over 80. Several genes have been linked to the condition -- particularly one that codes for a protein known as beta-amyloid peptide.

Mutations to this gene cause the protein to be overproduced, forming the bulk of the fibrous 'senile plaques' seen in the brains of Alzheimer's patients and killing nerve cells. When the corresponding mouse gene is altered, the animals develop certain hallmarks of the disease, including protein deposits.

Richard Morris of Edinburgh University in Scotland and colleagues have now discovered that such 'Alzheimer's-model' mice seem to suffer similar age-related mental problems to human patients1.

Last year4researchers showed that when such Alzheimer's mice are vaccinated with beta-amyloid peptide they develop antibodies against the protein which sweep the brain clean of the plaques. Now Peter St George-Hyslop of the University of Toronto in Canada and his colleagues and a second team led by Dave Morgan of the University of South Florida at Tampa show that the vaccine also reduces learning and memory loss as the mice age.

Each group gave Alzheimer's mice learning and memory tests, in which the animals had to swim to a submerged platform. In one trial the platform was moved each day, testing short-term memory. The second trial investigated 'spatial-reference' memory by leaving the platform in one place and testing the mice once a month.

Mice given the test vaccine developed fewer and smaller protein deposits in their brains and performed markedly better than unvaccinated animals in both types of memory test. These results are reported in Nature.

The really significant aspect of this work to me is not so much the result but the process they use," says Chapman. "Other treatment studies tend to create the pathology of Alzheimer's [the protein blobs] and then try to make them go away. Tests of behaviour like this are critical."

Whether the protein deposits actually cause dementia in people is something of an open question among Alzheimer's researchers. Some believe they do, and that preventing the deposits from forming should relieve the distressing mental symptoms, although others disagree. This work, Morgan says, supports the hypothesis that the two are related. But it does not prove anything because a combination of factors could still be involved.

"It is certainly encouraging and we are all hoping that some kind of human application follows," says John O'Keefe, a UK neuroscientist at University College London who studies the behavioural defects seen in Alzheimer's disease. However, the mouse models don't seem to show the same neural destruction suffered by human patients, he says. "So I think we're going to have to take a closer look at exactly what goes wrong in the brain before we can rectify it." 

  • References

    1. Chen,G. et al. A learning deficit related to age and beta-amyloid plaques in a mouse model of Alzheimer's disease. Nature 408, 975 - 979 2000. | Article | PubMed | ISI | ChemPort |
    2. Janus,C. et al. A beta-peptide immunisation reduces behavioural impairment and plaques in a model of Alzheimer's disease. Nature 408, 979 - 982 2000. | Article | PubMed | ISI | ChemPort |
    3. Morgan,D. et al. A beta-peptide vaccination prevents memory loss in an animal model of Alzheimer's disease. Nature 408 982 - 985 2000. | Article | PubMed | ISI | ChemPort |
    4. Schenk,D. et al. Immunisation with amyloid-beta attenuates Alzheimer's disease-like pathology in the PDAPP mouse. Nature 400, 173 - 177 1999. | Article | PubMed | ISI | ChemPort |