BINDING OF AMYLOID BETA-PROTEIN TO INTRACELLULAR BRAIN PROTEINS IN RAT AND HUMAN

Amyloid beta-protein (A beta), in its soluble form, is known to bind s everal circulatory proteins such as apolipoprotein (apo) E, apo J and transthyretin. However, the binding of A beta to intracellular protein s has not been studied. We have developed an overlay assay to study A beta binding to intracellular brain proteins. The supernatants from bo th rat and human brains were found to contain several proteins that bi nd to A beta 1-40 and A beta 1-42. No major difference was observed in the A beta binding-proteins from brain supernatants of patients with Alzheimer's disease and normal age matched controls. Binding studies u sing shorter amyloid beta-peptides and competitive overlay assays show ed that the binding site of A beta to brain proteins resides between 1 2-28 amino acid sequence of A beta. The presence of several intracellu lar A beta-binding (A beta B) proteins suggests that these proteins ma y either protect A beta from its fibrillization or alternatively promo te A beta polymerization. Identification of these proteins and their b inding affinities for A beta are needed to assess their potential role in the pathogenesis of Alzheimer's disease.