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AIDS dementia: neurons nixed by virus?

Almost one-third of all AIDS patients eventually develop encephalitis, or inflammation of the brain. As their encephalitis progresses, memory loss and other forms of dementia become increasingly severe. This has led scientists to suspect that AIDS dementia arises because the inflammation damages brain cells.

Now, evidence from an autopsy study suggests a more direct mechanism for these debilitating changes: The AIDS virus itself may destroy neurons in the fr ntal cortex of the brain.

Laboratory studies in recent years have shown that the AIDS virus, HIV, somehow manages to kill neurons in culture, even though it does not enter and infect them. Those findings spurred three British neuropathologists to determine whether the virus can, in the absence of encephalitis, inflict enough neuronal damage to cause dementia in people with AIDS. Ian P. Everall and his colleagues at the Denmark Hill Institute of Psychiatry in London tested their hypothesis by examining the frontal cortex, an area involved in though and reasoning, of 11 deceased AIDS patients and eight people who died of causes unrelated to AIDS or encephalitis.

The investigators used a newly developed tool called a dissector to calculate the density of neurons in three-dimensional sections of the frontal cortex samples. The neuron density in the AIDS patients' brains was almost 40 percent lower than in the non-AIDS brains, they found.

Although fluid from all of the AIDS brains harbored HIV, six of the 11 showed no signs of encephalitis. Moreover, the researchers discovered that the neuron density in those six brains was just as low as in the five encephalitic AIDS brains. This, they say, suggests that HIV alone can cause a loss of neurons.

Because Everall and his co-workers did not have access to the patients' clinical records, they do not know whether any of them actually had dementia. Nonetheless, they assert in the May 11 LANCET, "the cause of dementia in AIDS patients has to be reevaluated."

"This is the first investigation that has shown neuronal loss without HIV encephalitis," says coauthor Peter L. Lantos. Finding such a dramatic loss in a cortical area of the brain is especially significant, Everall adds, because a comparable degree of conical cell loss is associated with the severe dementia suffered by Alzheimer's patients.

"These types of losses are going to have a physiological impact," says Clayton A. Wiley, a pathologist at the University of California, San Diego.

Because the new study does not establish any clinical connection with dementia in encephalitis-free AIDS patients, Everall cautions that the findings do not prove that HIV causes dementia by killing neurons. He does, however, propose what he calls "a sensible and logical mechanism" by which the virus might kill cortical neurons directly. An HIV envelope protein called gp 120 may interfere with a brain peptide called VIP that some cortical neurons need in order to send electrical signals to one another, he told SCIENCE NEWS. Researchers already know that this peptide can, in the test tube, protect brain neurons from the toxic effects of gp 120, he adds.

Brynmor A. Watkins of the National Cancer Institute in Bethesda, Md., questions the British team's exclusive focus on the frontal cortex, which may have led them to overlook encephalitis in other brain parts, especially lower regions such as the basal ganglia and the cerebellum. Encephalitis in these subcortical regions correlates strongly with certain symptoms of AIDS dementia, such as limb weakness and poor coordination, he says. In addition, he argues that the six seemingly encephalitis-free AIDS patients may have had frontal-cortex inflammation at one time and that their encephalitis subsided before they died.
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Title Annotation:dementia may be caused by the AIDS virus destroying neurons in the frontal cortex
Author:Walker, Tim
Publication:Science News
Date:May 18, 1991
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