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Cerebral white matter damage in HIV infection demonstrated using beta-amyloid precursor protein immunoreactivity
F Raja1, F E Sherriff, C S Morris
1Department of Neurology, Radcliffe Infirmary, Oxford, UK.
Abstract:
We have examined brain sections from 55 autopsy cases of AIDS for the prevalence and severity of axonal damage, assessed using beta-amyloid precursor protein (beta APP) immunoreactivity as a marker of such damage. The cases were subdivided into cases with HIV encephalitis with multinucleated giant cells (MGC), cases with other specific pathology, such as cerebral toxoplasmosis or lymphoma, cases with non-specific pathology and cases with no pathology. Significantly more foci containing beta APP+ axons were found in cases with HIV encephalitis with MGC (80%) and in cases with other specific pathology (58%) than in those with non-specific (30%) or no pathology (30%). The prevalence and abundance of beta APP+ axons generally paralleled the severity of pallor of myelin staining of cerebral white matter in cases without other specific pathology but in 4 cases without any pallor of myelin staining beta APP+ axons were present, suggesting that it may be a more sensitive marker of some forms of white matter damage in HIV infection than myelin pallor. Foci of beta APP+ axons were found in subcortical and deep white matter but did not convincingly co-localise with foci of demonstrable HIV infection as indicated by the presence of MGC and HIV p24 immunoreactivity. In contrast, they showed an approximately perivascular distribution at some sites in all of the disease categories studied. We consider this localisation to be more suggestive of a vascular pathogenetic mechanism of deep white matter damage in HIV infection than a mechanism dependent on diffusion of local myelinotoxic products from foci of cerebral HIV infection.
Insights
Beta-amyloid precursor protein (beta APP) indicates axonal damage in AIDS brains. This marker is more prevalent in HIV encephalitis and other specific pathologies, suggesting a vascular mechanism for white matter damage.
Area of Science:
- Neuroscience
- Neuropathology
- Infectious Diseases
Background:
- Acquired Immunodeficiency Syndrome (AIDS) can cause neurological complications.
- HIV-associated neurocognitive disorders (HAND) involve white matter damage.
- Beta-amyloid precursor protein (beta APP) is a marker for axonal injury.
Purpose of the Study:
- To investigate the prevalence and severity of axonal damage in AIDS autopsy brains.
- To assess beta APP immunoreactivity as a marker of axonal damage.
- To explore the pathogenetic mechanisms of white matter damage in HIV infection.
Main Methods:
- Examination of brain sections from 55 autopsy cases of AIDS.
- Subdivision of cases based on neuropathology: HIV encephalitis with multinucleated giant cells (MGC), other specific pathology, non-specific pathology, and no pathology.
- Assessment of beta APP immunoreactivity to identify axonal damage foci.
- Evaluation of myelin staining for white matter pallor.
- Analysis of co-localization with MGC and HIV p24 immunoreactivity.
Main Results:
- Significantly higher prevalence of beta APP+ axons in HIV encephalitis with MGC (80%) and other specific pathologies (58%) compared to non-specific (30%) or no pathology (30%).
- Beta APP+ axons generally correlated with myelin pallor, but were present even without myelin pallor in some cases, indicating higher sensitivity.
- Axonal damage foci were found in subcortical and deep white matter, with a perivascular distribution, not consistently co-localizing with HIV infection foci.
Conclusions:
- Beta-amyloid precursor protein (beta APP) is a sensitive marker for axonal damage in AIDS-related white matter injury.
- The perivascular distribution of axonal damage suggests a vascular pathogenetic mechanism in HIV infection.
- This contrasts with mechanisms involving diffusion of myelinotoxic products from HIV infection sites.