Sodium dodecyl sulfate-resistant complexes of Alzheimer's amyloid beta-peptide with the N-terminal, receptor binding domain of apolipoprotein E

Immunocytochemical, biochemical, and molecular genetic studies indicate tha t apolipoprotein E (apoE) plays an important role in the process of amyloid ogenesis-beta. However, there is still no clear translation of these data i nto the pathogenesis of amyloidosis-beta. Previous studies demonstrated sod ium dodecyl sulfate (SDS)-resistant binding of apoE to the main component o f Alzheimer's amyloid-A beta and modulation of A beta aggregation by apoE i n vitro. To more closely characterize apoE-A beta interactions, we have stu died the binding of thrombolytic fragments of apoE3 to A beta in vitro by u sing SDS-polyacrylamide gel electrophoresis and intrinsic fluorescence quen ching. Here we demonstrate that SDS-resistant binding of A beta is mediated by the receptor-binding, N-terminal domain of apoE3. Under native conditio ns, both the N- and C-terminal domains of apoE3 bind A beta; however, the f ormer does so with higher affinity. We propose that the modulation of A bet a binding to the N-terminal domain of apoE is a potential therapeutic targe t for the treatment of amyloidosis-beta.