Neuronal apoptosis does not correlate with dementia in HIV infection but is related to microglial activation and axonal damage

To characterize the distribution of apoptotic neurons and their relationshi ps with the stage of disease, a history of HIV-dementia, and the degree of productive HIV infection, microglial activation and axonal damage, we exami ned the brains of 40 patients. Samples of frontal and temporal cortex, basa l ganglia and brain stem were taken post-mortem from 20 patients with AIDS (including three with HIV-dementia, and eight with cognitive disorders that did not fulfil the criteria for HIV-dementia), 10 HIV-positive asymptomati c cases and 10 seronegative controls. Neuronal apoptosis was demonstrated b y in situ end labelling in 18 AIDS cases and two pre-AIDS cases; a single a poptotic neuron was present in the temporal cortex of a control. Semiquanti tative evaluation showed that the severity of neuronal apoptosis in the cer ebral cortex correlated with the presence of cerebral atrophy, but not with a history of HIV dementia. There was no global quantitative correlation be tween neuronal apoptosis and HIV encephalitis or microglial activation. How ever, there was some topographical correlation between these changes. In th e basal ganglia, apoptotic neurons were much more abundant in the vicinity of multinucleated giant cells and/or p24 expressing cells. Microglial activ ation was constantly present in these areas. Axonal damage was identified u sing beta-amyloid-precursor protein (beta APP) immunostaining in 17 AIDS an d eight pre-AIDS brains. Although no global quantitative correlation could be established between axonal damage and neuronal apoptosis there was an ob vious topographic correlation supporting the view that axonal damage, eithe r secondary to local microglial activation or due to the intervention of sy stemic factors, may also contribute to neuronal apoptosis.