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THURSDAY, June 26, 2003 (HealthDayNews) -- The buildup of toxic proteins in the brains of Alzheimer's patients is accompanied by changes in several genes linked to memory and learning, a new study has found.
The study, which looked at both mice and humans, found that brain cell genes known to regulate memory and learning were significantly suppressed in the presence of plaques composed of a renegade protein called beta-amyloid. Many Alzheimer's researchers believe these plaques cause the dementia and other mental decline that mark the condition.
Dave Morgan, an Alzheimer's expert at the University of South Florida in Tampa, and the leader of the study, says the work could open a new frontier in the search for therapies to fight the disease.
So far, scientists have come at Alzheimer's from three directions: drugs that block the buildup of protein deposits, "plaque-busting" drugs that break up the protein clusters and allow the brain to clear them away and vaccines that encourage the immune system to destroy the plaques.
The fourth way, Morgan says, would be to use the latest information and subsequent research to design drugs that could reverse the effects of beta-amyloid on brain genes.
"I don't know that these drugs would ever be useful by themselves," he says, but they could augment some or all of the other treatments. No such compounds are in development yet, Morgan adds.
A report on the findings appears in the latest issue of the Journal of Neuroscience.
An estimated four million Americans have Alzheimer's disease, a brain-wasting condition that has no cure. Treatments for the disorder can briefly delay, but not halt, its progression.
The researchers studied mice engineered with two genes that cause them to accumulate beta-amyloid plaques in their brain. These animals ultimately develop some of the neurological problems consistent with the human Alzheimer's disease.
Using a "gene chip," which identifies increases or decreases in the genetic activity of cells, the scientists discovered six genes in the brain tissue of the sick mice that were significantly suppressed in the presence of plaques.
The genes -- called Arc, Zif268, NR2B, GluR1, Homer-1a and Nur77/TR3 -- play key roles in learning and memory. Animals missing the first two "cannot remember anything," Morgan says. "With other research we've found 10 genes that are affected," including one for a vital enzyme that controls the electrical "heartbeat" of neurons, he adds.
Interestingly, the scientists say, the six genes reported in the current paper appeared to function normally in areas of the brain that weren't infiltrated by the protein deposits.
After confirming their results with a different gene-measuring technique, the group turned to tissue samples from the brains of people who'd died with Alzheimer's disease.
Again, the six learning and memory genes were muted in cells affected by beta-amyloid plaques. But unlike in the mice, a host of other brain genes also were suppressed.
Morgan says that's not a surprise because people who die with advanced Alzheimer's have suffered widespread death of neurons. As a result, all of the genes in their brain cells are likely to be affected.
The mice his group used don't experience neuron death. "We suspect that if we had obtained brain tissue of patients who had died very early in Alzheimer's disease, then the picture would have been much more similar" to what occurred in the animals, he says.
D. Stephen Snyder, who studies Alzheimer's at the National Institute on Aging, which funded the research, agrees that the findings could lead to new treatments for the disease.
"I think that's a reasonable, hoped-for outcome down the road," Snyder says. However, he adds, trying to control the individual genes affected by plaques would perhaps be "more difficult to manage" than other approaches.
More information
Try the Alzheimer's Association or the National Institute on Aging for more on Alzheimer's disease.
