ACCUMULATION OF BETA-AMYLOID PRECURSOR

The pathogenesis of neuropsychological abnormalities in patients with human immunodeficiency virus type 1 (HN-B) encephalitis is obscure bec ause neurons are nor the target of infection and severe neuronal loss occurs only late during the disease. Moreover, there is evidence indic ating that HIV dementia is not a homogeneous entity and could partiall y reverse after treatment with zidovudine, The finding that impaired a xonal flow, evidenced by beta-amyloid precursor protein immunoreactivi ty, could contribute to the neuropsychological deficits prompted the p resent study. Brains of patients with full-blown acquired immunodefici ency syndrome (AIDS) were studied and findings compared with those of normal and abnormal control subjects. The presence of HIV-1 DNA was in vestigated by nested polymerase chain reaction; axonal abnormalities w ere detected by beta-amyloid precursor protein, ubiquitin immunohistoc hemistry, and silver staining. Accumulation of beta-amyloid precursor protein was observed in all the HIV encephalitis brains studied; the a ppearance of the immunostaining varied from globular structures to bun dles of parallel formations. In 2 AIDS brains without pathological abn ormalities, only the latter pattern was detected. The brains with trau ma mere strongly reactive with beta-amyloid precursor protein antibody and the different reactivity within them correlated with posttrauma s urvival, only globular structures being detected in the older cases. N o correlation was found between the different pattern of beta-amyloid precursor protein reactivity and dementia in AIDS patients. These resu lts shaw that widespread axonal injury is a constant feature in AIDS b rains and suggest that it could play a role in the pathogenesis of the neuropsychological abnormalities of these patients.