Sodium Dodecyl Sulfate-Resistant Complexes of Alzheimer’s Amyloid β-Peptide with the N-Terminal, Receptor Binding Domain of Apolipoprotein E

Immunocytochemical, biochemical, and molecular genetic studies indicate that apolipoprotein E (apoE) plays an important role in the process of amyloidogenesis- β. However, there is still no clear translation of these data into the pathogenesis of amyloidosis- β. Previous studies demonstrated sodium dodecyl sulfate (SDS)-resistant binding of apoE to the main component of Alzheimer’s amyloid-A β and modulation of A β aggregation by apoE in vitro. To more closely characterize apoE-A β interactions, we have studied the binding of thrombolytic fragments of apoE3 to A β in vitro by using SDS-polyacrylamide gel electrophoresis and intrinsic fluorescence quenching. Here we demonstrate that SDS-resistant binding of A β is mediated by the receptor-binding, N-terminal domain of apoE3. Under native conditions, both the N- and C-terminal domains of apoE3 bind A β; however, the former does so with higher affinity. We propose that the modulation of A β binding to the N-terminal domain of apoE is a potential therapeutic target for the treatment of amyloidosis- β.