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Half of AIDS dementia cases are associated with HIV-encephalitis or myelin pallor. Another half die with no HIV-related neuropathological changes. Previous observations suggest that cerebral dysfunction may result from more subtle cellular interactions, and that some of them may be mediated by cell adhesion molecules. In the present study the expression by astrocytes and endothelial cells of intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) was analysed as a function of the neuropathological diagnosis, the density of astrogliosis and of HIV-1 positive cells, and of the mental status. Twelve AIDS cases, without focal brain lesion, eight of whom were demented. were selected from a prospective study. They were compared with six control cases with multiple sclerosis, and with six control patients without neurological disease. ICAM-1 and VCAM-1 expression was localized by immunofluorescence and confocal microscopy. HIV protein gp41 1 was detected by immunohistochemistry on adjacent sections. Endothelial expression of ICAM-1 and VCAM-1 was significantly up-regulated in all AIDS patients. VCAM-1 only was related to myelin pallor. The density of VCAM-1 or ICAM-1 positive astrocytes increased in demented AIDS patients, independently of the neuropathological findings or the density of gp41 positive cells. Expression of cell adhesion molecules, together with other secondary mechanisms such as secretion of cytokines may play a role in the pathogenesis of white matter lesions leading to HIV-1-associated cognitive changes.