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Alzheimer's disease therapeutic prevents long-term damage from TBI in pre-clinical studies
Date:3/15/2009

ent form of cell death, and can result in large holes in brain tissue that cause lasting neurological effects. To date, there has been no way to prevent or treat this damage, he says.

In this study, the investigators sought to understand if amyloid peptide contributed to secondary injury. Amyloid peptides are produced when a long protein in the brain known as the amyloid precursor protein (APP) is cut in two by the enzyme beta secretase, and then cut into smaller pieces by a second enzyme, known as gamma secretase.

The researchers went on to test Alzheimer's disease amyloid-busting agents as a brain injury treatment. It worked. "By using a gamma secretase inhibitor, we prevented much of secondary traumatic brain injury in mice in our experiments," he says.

To look at the role of amyloid in brain injury, the researchers used two different approaches to blocking activation of the pathway that produces amyloid peptide. They used a group of mice that were genetically altered so that they did not produce any beta secretase, which meant they were incapable of producing amyloid.

They also treated "normal" mice with the experimental agent DAPT, one of the first gamma secretase inhibitors developed and the model upon which some Alzheimer's disease drugs now in clinical testing are based. As a result, amyloid peptide production was substantially reduced in this group.

They first showed that in a group of normal control mice, brain injury produced substantially more amyloid peptide, and that the brain region known as the hippocampus, which is also affected in Alzheimer's disease, was substantially damaged.

They then followed the groups of reduced amyloid mice after injury, and found that three weeks after initial trauma, both groups performed almost equally well on learning tests. Magnetic resonance imaging scans of the mice showed that these two groups of mice did not have "nearly the same amount of damage in the hippo
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Contact: Karen Mallet
km463@georgetown.edu
215-514-9751
Georgetown University Medical Center
Source:Eurekalert

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