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AIDS DEMENTIA: MISPLACED BLAME?

By Robert Root-Bernstein

Science News 31 Aug. 1991


The notion that AIDS dementia is caused by HIV infection of brain neurons ("AIDS dementia: Neurons nixed by virus?" SN: 5/18/91, p.311) is unlikely for four reasons.

First. unlike other viruses that attack the central nervous system. HIV has no known tropism for neurons. Second. HIV generally requires the CD4 receptor of T­helper cells and macrophages to enter a cell, but neither the CD4 protein nor any similar protein exists on neurons. Third, viruses do not usually have access to the brain until the blood­brain barrier has been breached. Fourth. and most important, the same sorts of dementias seen in AIDS patients also occur in other immunosuppressed people, proving that HIV is not a necessary cause. Once the blood­brain barrier has been breached, any infection can-and in AIDS patients often does - get in. Cytomegalovirus, herpes simplex viruses, cryptococcus and toxoplasmosis are very frequently isolated from the central nervous systems of AIDS patients.

For these reasons, I proposed a radically different explanation of AIDS dementia last year. Animal models of diseases that cause nervous system destruction have existed for nearly a century and their pathology mimics many aspects of AIDS dementia, including demyelinization and neuron death. To induce these experimental diseases, an immunestimulating bacterial "adjuvant" and a protein mimicking one found in the nervous system (such as myelin basic protein) are combined and inoculated into an animal. Neither alone is sufficient to cause the disease process, but in combination they produce an autoimmune reaction that destroys the blood­brain barrier and then destroys the myelin sheaths and neurons.

Autopsy records of patients with dementias involving demyelinization-a large proportion of dementia patients-almost always reveal a combination of bacterial (usually mycobacterial) and herpesvirus (usually cytomegalovirus) infections. People who do not develop such dementias have one or neither infection. but almost never both.

The importance of these observations for understanding AIDS dementia is fourfold. First, the known prerequisites for producing nervous system destruction in animals exist in both AIDS and non­AIDS dementia, but not in people who are spared this problem. Second, there is no correlation between dementia and the presence of HIV, since HIV is present in virtually every AIDS patient, with or without dementia. Third, once the blood­brain barrier has been breached by the autoimmune process, HIV (and many other infectious agents) have access to the central nervous system. explaining the frequent isolation of the virus without implicating it directly in the dementia. And fourth, if my explanation is correct, then antimycobacterial and antiherpesvirus treatments should protect many HlV­positive patients from developing dementia.*

Robert S. Root­Bernstein
Associate Professor of Physiology Michigan State University East Lansing. Mich.


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