Study Fingers Alzheimer's Culprit
Study Fingers Alzheimer's Culprit
Feb. 29, 2000 (Atlanta) -- In their search for the culprit behind Alzheimer's disease, researchers report finding the smoking gun. Studies released today suggest that a specific brain protein sets in motion the series of events that leads to the brain degeneration seen in people with Alzheimer's disease.
The hallmark feature of Alzheimer's disease is the accumulation of a type of plaque in the brain. However, the new research shows that mice genetically engineered to develop these plaques only do so if they also have the genes for a protein called apolipoprotein (apoE). Moreover, mice with a type of apoE associated with high risk for Alzheimer's -- apoE4 -- developed 10 times more plaques. This study not only highlights the danger of high levels of apoE4, but also shows that the protein is an essential contributor to the Alzheimer's disease process.
"I think this study goes as far toward showing that apoE is required for [Alzheimer?s disease] as you can go," study leader David M. Holtzman, MD, tells WebMD.
Co-author Steven M. Paul, MD, vice president of Lilly Research Laboratories, tells WebMD that the findings are of particular relevance to human disease. "What's exciting about the finding is that ? this form of the protein is [speeding up the disease process]," he says.
The findings offer hope that drugs targeted at apoE could prevent Alzheimer's disease. This will not be a straightforward process: Outside the brain, the protein keeps cholesterol from clogging up the bloodstream.
"ApoE plays a very important role in the body -- if you don't have it, you have incredibly high cholesterol levels in the blood," says Holtzman, associate professor of neurology at Washington University School of Medicine in St. Louis. "But in the normal brain, it's not really clear if apoE is necessary. Most workers have not found anything significantly wrong in the brains [of mice that don't have] apoE, and in humans lacking an apoE gene there is no report of [dementia]."
These findings suggest that drugs able to regulate apoE in the brain might not have serious adverse effects -- as long as they do not affect apoE in the blood. "That's the trick," Paul says. "We think there is a way. Lilly is investigating whether it would be possible to alter apoE levels specifically in the brain."
The hallmark feature of Alzheimer's disease is the accumulation of a type of plaque in the brain. However, the new research shows that mice genetically engineered to develop these plaques only do so if they also have the genes for a protein called apolipoprotein (apoE). Moreover, mice with a type of apoE associated with high risk for Alzheimer's -- apoE4 -- developed 10 times more plaques. This study not only highlights the danger of high levels of apoE4, but also shows that the protein is an essential contributor to the Alzheimer's disease process.
"I think this study goes as far toward showing that apoE is required for [Alzheimer?s disease] as you can go," study leader David M. Holtzman, MD, tells WebMD.
Co-author Steven M. Paul, MD, vice president of Lilly Research Laboratories, tells WebMD that the findings are of particular relevance to human disease. "What's exciting about the finding is that ? this form of the protein is [speeding up the disease process]," he says.
The findings offer hope that drugs targeted at apoE could prevent Alzheimer's disease. This will not be a straightforward process: Outside the brain, the protein keeps cholesterol from clogging up the bloodstream.
"ApoE plays a very important role in the body -- if you don't have it, you have incredibly high cholesterol levels in the blood," says Holtzman, associate professor of neurology at Washington University School of Medicine in St. Louis. "But in the normal brain, it's not really clear if apoE is necessary. Most workers have not found anything significantly wrong in the brains [of mice that don't have] apoE, and in humans lacking an apoE gene there is no report of [dementia]."
These findings suggest that drugs able to regulate apoE in the brain might not have serious adverse effects -- as long as they do not affect apoE in the blood. "That's the trick," Paul says. "We think there is a way. Lilly is investigating whether it would be possible to alter apoE levels specifically in the brain."
Source...