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Tuesday, August 16, 2011

Understanding AIDS-related dementia

Although treatments for HIV have improved dramatically, about half of HIV patients still suffer some form of cognitive deficiency.  Up to 5% develop dementia.  Researchers from Albert Einstein College of Medicine and from Johns Hopkins now believe they know whyHIV infection is compromising the blood-brain barrier.

The blood-brain barrier is composed of endothelial cells which are packed much more tightly than in the rest of the body.  Any molecule that makes its way into the brain must first pass through these tight junctions. This effectively protects the brain from pathogens or large molecules.  Astrocytes make up an important cellular support system for the endothelial cells.

The scientists, led by Joan Berman, found that HIV-infected astrocytes can compromise the integrity of the blood-brain barrier.  The infected astrocytes both passively allowed their endothelial clients to die, and emitted toxic signals killing neighboring astrocytes.  Both events lead to gaps in the blood-brain barrier, which may in turn be the cause of the neurological problems.

Not surprisingly, this work has not been done in humans, but in macaque monkeys and in human cells.  Nevertheless, the authors suggest that treatments that protect astrocytes may reduce HIV-related dementia.