By crossing two strains of mice that are now used to study Alzheimer's, researchers from the Mayo Clinic in Jacksonville, Fla., have created an even better animal model of the disease. The new mice succumb to all the symptoms of their parents. From one side, they inherit a mutation in the gene encoding the amyloid precursor protein (APP) and as a result develop amyloid plaques. From the other parent, they bear mutations in the tau-protein gene and thus exhibit tau-related neurofibrillary tangles. And as such, these animalsa strain christened TAPP for tau and APPare the first to develop both of the hallmark brain lesions seen in human Alzheimer's disease.
The researchers hope the TAPP mice will shed light on the development of Alzheimer's and, specifically, whether the plaques lead to the tangles or vice versa. "What we saw in the crossbred mice were not only plaques and tangles, but the tangle pathology was enhanced in regions where the plaques occurred," Mayo scientist Michael Hutton explains. "If we were simply seeing random changes in the tangle pathology in areas that weren't related to amyloid or Alzheimer's disease, this would not be so interesting. The key point is we see the enhanced tangle pathology in areas that are affected in Alzheimer's."
For the moment, the scientists have started testing the amyloid vaccine, announced this past December, on the TAPP animals and hope to refine the mouse model even further. "One of the biggest problems we have is that the tau mice don't live all that long," Hutton says. "They start to die at an age when the pathology in the amyloid mice hasn't reached its final stage." To solve the problem, the team is trying to engineer mice that deposit amyloid plaques more quickly. "This will basically let us compress the time frame of these studies," Hutton adds, "allowing us to look at mice that have lots of amyloid together with tau pathology, and to do it all within the life span of these crossed animals."
