Ratios predict risk
Dr. Younkin joined a core group of researchers and physicians at Mayo Clinic already collaborating to study the basic biology of the disease and methods of caring for patients who have the disorder. Based on the knowledge that Alzheimer’s is a disease of tau tangles as well as AB plaque, these scientists were already developing a mouse that spontaneously overproduces tau proteins.
Mayo Clinic researchers were the first to genetically engineer a mouse to express a mutation of the gene that controls tau production, and in 2000 they reported in Nature Genetics that the “tau” mouse develops the same kind of neurofibrillary tangles seen in human dementia. In 2001, the Mayo Clinic team produced another new engineered mouse, the first to exhibit tangles as well as the two forms of plaque (AB40 and AB42). In the journal Science, Michael Hutton, Ph.D., Dennis Dickson, M.D., Jada Lewis, Ph.D., Shu-Hui Yen, Ph.D., and Eileen McGowan, Ph.D., presented the mouse model, saying it is the best animal model possible to test therapies aimed at slowing down, or halting, neurodegeneration.
The engineered mouse strengthened the notion that development of tangles followed that of plaque. The tangle pathology was enhanced in regions where the plaque occurred, says Dr. Hutton, a neurobiologist. But what was also interesting was that these mice, the ones that also developed plaque, produced more tau than did mice with only a tau mutation. “That proved that there is an interaction between tau and amyloid, and it is that interaction that causes cognitive deficits,” he says.
These Mayo mice are offered to any scientist studying Alzheimer’s disease for just the cost of producing them. They are also made available to pharmaceutical companies to help them test whether the drugs they are developin