This project was undertaken to elucidate biochemical and immunological aspects of myelin disorders associated with neuro-AIDS including myelin pallor, vacuolar myelopathy and multifocal demyelination in the CNS as well as demyelinating peripheral neuropathy. Postmortem CNS tissue from AIDS patients being analyzed for quantitative and qualitative alterations of myelin proteins, including myelin-associated glycoprotein, myelin basic protein, proteolipid protein and 2',3'-cyclic nucleotide 3'- phosphodiesterase. The biochemical results are being correlated with histological and immunocytochemical observations made by our collaborators at Johns Hopkins University on adjacent sections of tissue. So far neither the biochemical analyses nor the immunocytochemical staining of white matter of AIDS CNS has suggested substantial loss of myelin proteins in areas where there is prominent myelin pallor. Our preliminary biochemical data on a limited number of samples demonstrated a loss of myelin proteins in only one of the AIDS samples, and this may have represented an area of local demyelination. Thus, it appears that myelin loss in neuro-AIDS may not be as wide-spread as suggested by traditional histological stains. Some of the immunocytochemical results suggest that the histochemical staining abnormalities in white matter of AIDS patients may relate to breakdown of the blood-brain barrier. Treatment of cultured oligodendrocytes with purified GP120 did not give evidence of cytotoxicity as had been reported for the treatment of neurons with this protein. In our previous studies on antibodies to ganqliosides in the inflammatory peripheral neuropathies, one patient with. high levels of serum antibodies to G(D1b) ganglioside was HIV-positive. Thus far, we have not detected anti-ganglioside antibodies in a very limited number of additional AIDS patients with neuropathy.
