The pathogenesis of neuropsychological abnormalities in patients with human immunodeficiency virus type 1 (HIV-1)
encephalitis is obscure because neurons are not the target of
infection and severe neuronal loss occurs only late during the disease. Moreover, there is evidence indicating that
HIV dementia is not a homogeneous entity and could partially reverse
after treatment with
zidovudine. The finding that impaired axonal flow, evidenced by
beta-amyloid precursor
protein immunoreactivity, could contribute to the neuropsychological deficits prompted the present study. Brains of patients with full-blown
acquired immunodeficiency syndrome (
AIDS) were studied and findings compared with those of normal and abnormal control subjects. The presence of HIV-1
DNA was investigated by nested polymerase chain
reaction; axonal abnormalities were detected by
beta-amyloid precursor
protein,
ubiquitin immunohistochemistry, and
silver staining. Accumulation of
beta-amyloid precursor
protein was observed in all the HIV
encephalitis brains studied; the appearance of the immunostaining varied from globular structures to bundles of parallel formations. In 2
AIDS brains without pathological abnormalities, only the latter pattern was detected. The brains with
trauma were strongly reactive with
beta-amyloid precursor
protein antibody and the different reactivity within them correlated with posttrauma survival, only globular structures being detected in the older cases. No correlation was found between the different pattern of
beta-amyloid precursor
protein reactivity and
dementia in
AIDS patients. These results show that widespread axonal injury is a constant feature in
AIDS brains and suggest that it could play a role in the pathogenesis of the neuropsychological abnormalities of these patients.