Cerebral white matter damage in HIV infection demonstrated using β-amyloid precursor protein immunoreactivity

• Published in: Acta neuropathologica 1997-02, Vol.93 (2), p.184-189
• Main Authors: RAJA, F, SHERRIFF, F. E, MORRIS, C. S, BRIDGES, L. R, ESIRI, M. M
• Format: Article
• Language: English
• Subjects: Acquired Immunodeficiency Syndrome - metabolism; Acquired Immunodeficiency Syndrome - pathology; Adolescent; Adult; Aged; AIDS/HIV; Alzheimer's disease; Amyloid beta-Protein Precursor - chemistry; Amyloid beta-Protein Precursor - immunology; Amyloid precursor protein; Autopsy; Axons; Axons - chemistry; Axons - pathology; Biological and medical sciences; Cerebral Cortex - chemistry; Cerebral Cortex - pathology; Encephalitis; Encephalitis, Viral - metabolism; Encephalitis, Viral - pathology; Giant cells; HIV; HIV Infections - metabolism; HIV Infections - pathology; Human immunodeficiency virus; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunohistochemistry; Immunopathology; Immunoreactivity; Infections; Lymphoma; Male; Medical sciences; Middle Aged; Myelin; Pathology; Substantia alba; Toxoplasmosis; β-Amyloid
• ISSN: 0001-6322; 1432-0533
• DOI: 10.1007/s004010050601

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.