Man's Rare Condition Upends Strategy Against Alzheimer's

Tuesday, 12 Aug 2014 08:12 AM

 

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A man with a rare disease has shown scientists that there might be a different way to try to halt the devastating damage of Alzheimer's disease.
 
A mutation of the apolipoprotein E gene (apoE4) has been shown to raise the chances of developing the memory-robbing condition, and experts have wondered how dangerous it would be to treat the patients by eliminating the protein from the brain. Now, researchers report, the answer might lie in the unusual case of an ill man whose body doesn't produce the protein at all.
 
While the man has a variety of medical problems linked to a rare disease, his lack of the protein doesn't appear to have hurt his brain.
 
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That medical fact might mean that lowering levels of the protein in the brain "may provide a wholly new venue for intervention in Alzheimer's disease. Our observations on this patient suggest that this strategy may now be entertained seriously," said study co-author Dr. Mary Malloy. She is director of the Pediatric Lipid Clinic at the Cardiovascular Research Institute at the University of California, San Francisco.
 
She said patients with Parkinson's disease and even brain injuries from concussions could benefit from the finding since it seems to apply to other kinds of brain disorders.
 
The discovery is reported online Aug. 11 in the journal JAMA Neurology.
 
ApoE4 "chaperones" certain kinds of proteins out of the brain. A fairly common genetic mutation connected to the protein boosts the risk of Alzheimer's disease. According to the U.S. National Institute on Aging, the mutation is found in 25 percent to 30 people percent of people overall and 40 percent of those with late-onset Alzheimer's.
 
One treatment might be to eliminate the protein in the brain to treat patients with Alzheimer's disease, and studies in animals have suggested this approach might work, said Dr. Joachim Herz. He is distinguished chair in Alzheimer's disease research at University of Texas Southwestern Medical Center, who wrote a commentary accompanying the study findings.
 
To find answers about the role of apoE and the cost of reducing its levels in the brain, the study authors turned to a 40-year-old man who sought treatment for an unusual disorder at UC San Francisco. He has no apoE and suffers from a condition known as dysbetalipoproteinemia, which disrupts his body's processing of cholesterol and causes painful growths known as xanthomas, when fat gathers under the skin.
 
The man, who's at higher risk of heart disease because of his condition, appears to be "cognitively normal," Herz said, meaning that his brain works properly. "The findings in this patient indicate that completely removing apoE would have no overt ill effects on brain function, and so an Alzheimer's treatment that reduced brain apoE would theoretically have no or little cognitive side effects," Herz said.
 
In addition, the study suggests that the lack of the protein doesn't affect the eye, where it's also found.
 
Why would a person be able to get by without the protein in the brain? Wouldn't the brain fail to work properly? It appears that one or more other proteins pick up its work, study co-author Malloy said. "Many metabolic processes are highly redundant."
 
There are caveats to the research. For one thing, the patient is 40 and it's not clear how aging will affect the functioning of his brain, an important consideration considering how Alzheimer's strikes seniors, commentary author Herz said.
 
Special: 4 Easy Ways to Keep Your Mind Sharp

And, he added, "the main potential side effect of reducing apoE would be the effect on cholesterol and triglyceride levels. This patient had extremely high levels of both -- something we would have to avoid when treating patients. It would obviously not be beneficial to reduce the risk for Alzheimer's disease if in the process we increase the risk for cardiovascular disease."
 
Still, he said, scientists are already working on a drug to lower the levels of the protein in humans. The research is in its early stages.

© HealthDay

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