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Jefferson scientists find how HIV causes dementia

Ever since the AIDS epidemic began more than two decades ago, scientists have been trying to understand why as many as one-quarter of those infected with HIV develop dementia.

Now, researchers at Jefferson Medical College may have an answer.

Investigators led by virologist Roger J. Pomerantz, M.D., director of the Division of Infectious Diseases and Environmental Medicine at Jefferson Medical College of Thomas Jefferson University in Philadelphia, have shown that the virus produces proteins that turn on specific biochemical pathways in the brain, leading to brain cell death.

Dr. Pomerantz and his co-workers report their results April 19 in an early online edition of the Proceedings of the National Academy of Sciences.

According to Dr. Pomerantz, professor of medicine, biochemistry and molecular pharmacology and director of the Center for Human Virology and Biodefense at Jefferson Medical College, researchers have been trying for more than two decades to find an explanation for why and how HIV causes "neuronal drop out" and dementia.

He explains that HIV in the brain causes hardly any inflammation or white blood cell increase, unlike in other brain infections, such as in meningitis or herpes infection.

"Neurons die," he says, "and the brain atrophies. It's extremely unusual. Infectious agents don't do this, but HIV does." He notes that the effect "is clearly due to HIV." In patients taking the anti-retroviral HAART cocktail of drugs, which halts retroviral replication, fewer individuals develop dementia than those who do not take the drugs.

"The overarching hypothesis has been that HIV infects brain cells called macrophages and microglia," he explains. These cells produce an array of substances called cytokines and chemokines, which kill neurons. "It's thought that HIV doesn't kill neurons directly, but rather, it's due to what the macrophages and microglia make."

Dr. Pomerantz and his group decided to find out wheth
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Contact: Steve Benowitz
steven.benowitz@jefferson.edu
215-955-5291
Thomas Jefferson University
19-Apr-2004


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