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Brain inflammation may be friend, not foe, for Alzheimer's patients

ontrol over brain levels of a human molecule known as interleukin-1beta, a well-recognized molecular kingpin in the realm of inflammation.

IL-1 beta, a signaling molecule that promotes brain inflammation, was one of the first molecules that scientists found in higher levels in the brains of people with Alzheimer’s disease compared to healthy people. It’s recognized as a critical player in bringing about much of the brain damage that follows a stroke and brain injury, so it’s no surprise that its presence in the brains of Alzheimer’s patients would be assumed to be part of the problem.

In the original development of his mouse, Shaftel worked closely with Stephanos Kyrkanides, D.D.S., Ph.D., associate professor in the Eastman Department of Dentistry and an expert on using a class of viruses known as lentiviruses for use in gene therapy. The team used a lentivirus to boost levels of IL-1 beta in select brain regions of its engineered mouse, then applied the technology in mice specially designed to develop Alzheimer’s disease.

The mice developed normally for six months. Then Shaftel raised the level of IL-1beta in one part of the brain –the hippocampus, an area of the brain that specializes in memory and one of the first parts of the brain to be affected by the disease – and followed the mice for an additional month, watching for effects in the brain regions that were awash in higher-than-normal levels of IL-1beta. It’s the first use of an organism where scientists can boost IL-1beta in select areas and then watch what happens as the process unfolds.

The team expected to see the telltale clumps of material known as amyloid plaques, made up of the peptide amyloid beta, worsen. Instead, to the team’s surprise, the brains of the mice with IL-1beta stuck in overdrive had only about half as many plaques as mice without the over-active IL-1beta.

Through extensive experiments, the team showed that the mice simply weren’t making
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Source:University of Rochester Medical Center


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