Apolipoprotein E distribution among different plaque types in Alzheimer's disease: implications for its role in plaque progression

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Abstract
We sought to determine the pattern of ApoE immunoreactivity in mesial temporal lobe tissue from 12 Alzheimer patients, age 66–88, and to determine the distribution of this immunoreactivity among different plaque types representing hypothesized stages of plaque evolution. In these patients, the cortical area of ApoE immunoreactivity was 30% that of β-amyloid. Only 6% of diffuse non-neuritic amyloid deposits were even weakly ApoE immunoreactive (ApoE+). This is in contrast to our previous demonstration that microglia overexpressing interleukin-1 (IL-1) are present in most diffuse non-neuritic deposits. Eighty-three per cent of diffuse neuritic plaques and 86% of dense-core neuritic plaques were highly ApoE+, consistent with IL-1–induced astrocyte activation and synthesis of ApoE, resulting in the appearance of ApoE immunoreactivity in neuritic plaques. Dense-core non-neuritic (‘burned out’) plaques were only rarely (6%) ApoE+. These results, together with the known trophic and toxic effects of ApoE on neurites, suggest that plaque-associated ApoE contributes to the formation of overgrown degenerating (dystrophic) neurites in plaques. However, the fact that some neuritic plaques are not ApoE+ suggests contributions by additional trophic and toxic factors. Our results are also consistent with a role for ApoE in the condensation of diffuse amyloid deposits into a β-pleated-sheet form that occurs concomitant with dystrophic neurite formation in the neuritic β-amyloid plaques of Alzheimer's disease.