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Researchers Find Many Head Injuries May Lead to Alzheimer's Disease

  [ 36 votes ]   [ Discuss This Article ] • January 30, 2002

Researchers at the University of Pennsylvania School of Medicine have found direct evidence that mild repetitive head injuries can lead to Alzheimer's disease. These findings could serve as a model in screening new drugs to treat Alzheimer's and traumatic brain injuries. The study is published in the January 15, 2002 issue of The Journal of Neuroscience.

According to Kunihiro Uryu, Ph.D., a senior research investigator at Penn's Center for Neurodegenerative Disease Research (CNDR), brain trauma accelerates Alzheimer's disease by increasing free radical damage and the formation of plaque-like deposits of Amyloid beta (Ab) proteins.

"This is the first experimental evidence linking head injuries to Alzheimer's disease by showing how repetitive concussions can speed up the progress of the disease," Uryu said.

While there are a number of documented genetic risk factors that predispose a person to Alzheimer's disease, head trauma has been identified as one very likely environmental factor.

Using mice implanted with the human gene responsible for the production of the Ab protein, Uryu and his colleagues were able to study how mild repetitive head injuries could influence the progress of Alzheimer's disease. Even without head trauma, these mice would eventually develop Ab plaques later in life. With the trauma, they produced symptoms of Alzheimer's disease at a remarkably increased rate.

"Here, we can clearly see a direct cause and effect relationship between repetitive concussions and Alzheimer's," said John Q. Trojanowski, M.D., Ph.D., co-director of the CNDR and professor in the Department of Pathology and Laboratory Medicine. "Using the head trauma model in these mice represents a step forward in our ability to understand the basic molecular mechanisms behind Alzheimer's disease. More importantly, we believe this model system can be used to screen for new medications in the search for a cure."

Over the course of the study, the mice were sedated and given mild repetitive concussions. Uryu and his colleagues then monitored the behavior and brain pathology of the mice. In addition to looking for deposits of Ab, they also monitored amounts of a molecule called isoprostane. Last year, Penn researchers discovered that urine isoprostane levels serve as an indicator of the sort of free radical damage found in Alzheimer's disease.

"Two days after the injuries, and again at nine and sixteen weeks, we measured amyloid deposits and levels of isoprostanes and amyloid beta proteins," said Uryu, "At each point, we saw a dramatic increase of indicators for Alzheimer's disease in the mice that received repetitive head traumas.

The findings suggest repetitive, not single, mild traumatic brain injuries increased Ab deposition as well as levels of Ab and isoprostanes in the mice. The repetitive injuries brought about cognitive impairments, but did not interfere with the motor functions and dexterity of the mice.

"Alzheimer's disease has a very real and understandable molecular basis and it will be curable," said Trojanowski. "Developing a working animal model of how head trauma augments Alzheimer pathology, as we have in our studies here, is just one more step in reaching the inevitable treatment."

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