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Manipulating brain inflammation may help clear brain of amyloid plaques, Mayo Clinic researchers say
Date:10/22/2009

e had initiated these studies using our new in vivo model to confirm whether inducing inflammation in the brain would in fact exacerbate the disease," Dr. Das says.

The researchers used a technique known as "Somatic Brain Transgenesis" to increase expression of Interleukin-6 (IL-6), a cytokine that stimulates an inflammatory immune response in the brains of young mice predisposed to developing age-progressive amyloid plaques. This powerful technology allows researchers to express any gene of interest in specific parts of the body by tagging the gene onto Adeno-associated viruses, which are inert. In this way, they can study the function of any protein in the brain, and also test its potential therapeutic use.

They found that IL-6 triggered inflammation throughout the brain, and they expected to see a big buildup of plaque as well as damage to brain neurons. "Instead, to our surprise, we found that the inflammation prevented plaques from forming and cleared whatever plaque that was already there," Dr. Das says.

Given this unexpected result, they performed additional experiments using different strategies. "First, we expressed IL-6 in the brains of newly born mice that are yet to develop any amyloid plaques and, secondly, we expressed IL-6 in the brains of mice with pre-existing plaque pathology," he says. "In both these cases, we got similar results the presence of IL-6 leads to the clearance of amyloid plaques from the brain."

The researchers then performed experiments to determine how the amyloid plaques were removed from the brain. Their analysis revealed that the inflammation induced by IL-6 in the brain directed the microglia cells to remove the amyloid plaques from the brain. Microglial cells do this by phagocytosis. "They gobble up the plaque, which they 'see' as a foreign invader, and break it apart," Dr. Das says. Researchers also found that activated microglia cells were closely attached to the plaques and expressed pro
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Contact: Kevin Punsky
punsky.kevin@mayo.edu
904-953-2299
Mayo Clinic
Source:Eurekalert

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