Questions that could lead to the possible creation of a drug to prevent or arrest Alzheimer's disease are on the verge of being answered by scientists at Mayo Clinic Jacksonville and their genetically engineered mice.
The scientists' work in producing mice that develop the same brain abnormalities as people was discussed at last month's World Alzheimer's Congress 2000 in Washington and published last week in the journal Nature Genetics. The work is being hailed as a major step in the fight against Alzheimer's.
Stephen Snyder, an expert on the disease for the National Institute on Aging, said the Mayo team's work with the cross-bred mice was ground-breaking.
"They open up an avenue to lots and lots of research," Snyder said. "They represent, I think, a significant leap, a significant advance."
Ultimately, the mice could help scientists understand the relationship between the two things that happen in the brains of people with Alzheimer's.
Nerve cells become surrounded by protein deposits called plaque, formed by the beta amyloid protein.
And inside the nerve cells, stringy, malformed tangles of a protein called tau develop.
Scientists have puzzled for years over the relationship between the plaque and tangles. Will an attack on one stop the other? And what causes the death of the nerve cells, leading to memory loss and dementia?
"It's like the chicken or the egg. Which came first? That's what they're trying to find out right now," said Diantha Grant, executive director of the Northeast Florida chapter of the Alzheimer's Association.
With the Mayo mice, researchers for the first time will be able to study how and why the tangles form, track their progression and test therapies against them.
Even more importantly, the Mayo researchers have been breeding their mice in the past several months with a breed genetically engineered in 1996 to produce plaque deposits.
Michael Hutton, a Mayo neurobiologist who led the research team, said the cross-breeding is producing mice that get both plaque and tangles. Those mice will give scientists a complete picture of the Alzheimer's disease process, he said.
It is difficult to study how Alzheimer's develops in humans because people usually don't get symptoms until the plaque and tangles are already present. And, except for rare versions of the disease that run in a small number of families, there is no blood test to predict who will get the disease so that scientists could start taking images of their brains early in the disease's progression.
However, some research indicates a relationship between the amount of beta amyloid protein in a person's bloodstream and their risk of developing Alzheimer's.
The Mayo researchers say their research on the unique mice shows that plaque formations precede the tangles.
"It definitely matters which comes first," Snyder said. "If you're treating the tangles, when the process that created the tangles remains untreated, that doesn't get you anywhere."
Hutton declined to elaborate on the disease process in the cross-bred mice until the results are published.
"We see an interaction [between the tangles and plaque]," Hutton said. "The preliminary results are very exciting."
SEEKING A VACCINE
The research at Mayo has implications for ongoing work on a vaccine. Last year, Elan Pharmaceuticals announced it had developed a vaccine that cleared plaque deposits from the brains of the mice that were genetically engineered to develop plaque.
Human vaccine trials have begun.
"Within 18 months, we expect to have an answer -- if we treat the amyloid-tau mice with vaccine, can we block the whole disease process, rather than just the formation of amyloid?" Hutton said.
"We think amyloid is the start of the whole process. …