Attenuation of the neurotoxic effect of Aβ 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 Aβ amyloid peptide with great avidity in vitro and in the neuritic plaque. Potentially, binding of Aβ to apolipoprotein E could increase Aβ neurotoxicity. However, in hippocampal cultures, 0.1 μM apolipoprotein E eliminated the neurotoxicity of 10 μM Aβ. Neuronal rescue was dose-dependent and occurred even after 48 hours exposure to Aβ, but was overwhelmed by excess Aβ. Thus, interaction between these proteins does not directly increase Aβ neurotoxicity, and the role of ApoE in Alzheimer's diseasse remains to be elucidated.