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A new century of Alzheimer's disease research

time, plasma levels of AB40 either continued to increase or decline much slower than AB42.

Drs. Graff-Radford, Younkin and Crook found that a low level of AB42 and a higher level of AB40 in blood could be seen three to five years before symptoms of the disease occurred. From these data, the Mayo Clinic researchers determined a scale of ratios for determining when symptoms will begin: two, four, or eight to 10 years.

“This blood test reflects some of the risks of who is going to develop the disease and when it is going to show up,” says Dr. Graff-Radford. “The crucial point is that it could eventually offer us a predictive test.”

The Mayo Clinic team is continuing to “follow the blood” of 2,000 participants in Rochester, and 1,000 in Jacksonville.

But the researchers know that if their AB40/AB42 ratio blood test ultimately can predict who will develop Alzheimer’s disease, people won’t be interested in knowing their risk unless something can be done to reduce that risk.

A pill a day keeps Alzheimer’s away

In the late 1990s, Dr. Golde’s research group as well as other investigators discovered that compounds that inhibited production of AB actually inhibited AB40 more than AB42. As AB42 appeared to be the real culprit in Alzheimer’s, Dr. Golde was convinced that a systematic search for compounds that preferentially lowered AB42 would be successful. However, a two-year effort did not find such a compound.

Then in 2000, Dr. Golde and Eddie Koo, M.D., who worked at the University of California, San Diego, screened several nonsteroidal anti-inflammatory drugs (NSAIDs) at high concentrations. To their surprise, they found that while some NSAIDs, such as naproxen and aspirin, had no effect on AB42, others, such as ibuprofen and indomethacin, did.

The possible significance of this finding was immediately apparent, Dr. Golde says. Large population studies had hinted that people who have used NSAIDs had a l
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