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The mouse models helped provide a breakthrough discovery for the Mayo Clinic researchers.

Physicians at the three Mayo Clinic sites have been collecting blood from thousands of Alzheimer’s patients, as well as study participants who do not have the disease, to determine how blood chemistry changes over the years (see associated story, Defining Alzheimer’s disease risk with the help of thousands). With support from the National Institutes of Health, they had been examining blood serum for evidence of protein “markers” that could help predict which people would develop the disease over time. One marker is AB.

Although no one knows what the normal function of AB is, the Mayo Clinic researchers found that it could be measured in blood, and that levels of both AB40 and AB42 varied in people who developed the disease. What they discovered through this analysis, however, surprised them, says Neill Graff-Radford, M.D., who heads the ADRC’s Memory Disorder Clinic and has led the work on a blood test designed to predict a person’s risk of developing Alzheimer’s.

“Levels of both AB40 and AB42 in the blood rise as a person gets older, but then, in some people, AB42 decreases,” he says. Turning to the transgenic mice, the researchers found that as soon as plaque began to develop in the brain, levels of AB42 decreased in the blood and spinal fluid.

Drs. Graff-Radford and Younkin had expected aging and genetic-related overproduction of AB42 -- the insult that leads of Alzheimer’s development -- would be reflected in blood samples. But sitting together in a room, looking at the charts that lead statistician Julia Crook, Ph.D., put together, the researchers experienced a classic “a-ha” moment. They saw it. The researchers realized that levels of AB42 had dropped because the protein was being sopped up, absorbed, by quickly forming plaques. In contrast, they discovered that at the same
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