Alzheimer's patients suffer from two types of abnormalities in their brains, but until recently, scientists didn't know if they had anything to do with each other. Now, two studies show how the two interact, providing fresh clues to the origins of the devastating memory loss caused by the disease.
Some cells in the brains of Alzheimer's patients contain tangles of a protein called tau. Extracellular areas elsewhere in the brain contain deposits, or plaques, of a peptide called amyloid b. After debating for years which of these lesions was the principal cause of Alzheimer's, most researchers now agree that both contribute to the disease. But despite some small hints, they haven't been able to determine if, or how, the two interact. One barrier was the lack of animals with both plaques and tangles.
No longer. Double mutants have been created by neuroscientist Michael Hutton and his colleagues at the Mayo Clinic in Jacksonville, Florida. They crossed transgenic mice that make extra tau and mice that overproduce a key precursor of amyloid b. The new mice exhibit five to 10 times as many tangles as mice with only the tau mutation, the team reports in the 24 August issue of Science, suggesting that the amyloid b deposits somehow spur on the development of tangles.
A second paper in the same issue bolsters their case. Neuroscientist Roger Nitsch at the University of Zürich in Switzerland and his colleagues injected amyloid b into the brains of mice that overexpress tau. Again, the injected mice had five times as many tangles as controls. Although the researchers injected amyloid b into a brain region called the hippocampus, the excess tangles formed in the nearby amygdala. That suggests amyloid b may inflict damage at a distance.
The results provide the "most convincing proof" yet that the two lesions are linked, says neuroscientist Virginia Lee at the University of Pennsylvania in Philadelphia. The new transgenic mice will be very valuable for Alzheimer's research, adds Harvard neuroscientist Mel Feany. "It's a tremendous piece of work," she says. Tests of a vaccine against amyloid b (ScienceNOW, 11 July 2000) are already under way in the new mice.