Attenuation of the neurotoxic effect of A beta amyloid peptide by apolipoprotein E.
Alzheimer's disease patients have increased frequency of apolipoprotein E allele c4, suggesting apoE4 is a risk factor determining disease. ApoE binds A beta amyloid peptide with great avidity in vitro and in the neuritic plaque. Potentially, binding of A beta to apolipoprotein E could increase A beta neurotoxicity. However, in hippocampal cultures, 0.1 microM apolipoprotein E eliminated the neurotoxicity of 10 microM A beta. Neuronal rescue was dose-dependent and occurred even after 48 hours exposure to A beta, but was overwhelmed by excess A beta. Thus, interaction between these proteins does not directly increase A beta neurotoxicity, and the role of ApoE in Alzheimer's disease remains to be elucidated.
Whitson, JS; Mims, MP; Strittmatter, WJ; Yamaki, T; Morrisett, JD; Appel, SH
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