CHARACTERIZATION OF APOLIPOPROTEIN J-ALZHEIMERS A-BETA INTERACTION

The main component of Alzheimer's amyloid deposits, A beta, has been found also as a soluble (sA beta) normal constituent of biological fluids and cell culture supernatants. Whether or not sA beta is the immediate precursor of A beta, it is clear that peptides with the same amino acid sequence can have both fibrillar and non-fibrillar conformations. The interconversion mechanism from one form to another is presently under intensive investigation. We have previously described that (i) a synthetic peptide A beta(1-40) immobilized on affinity matrices was able to retrieve apolipoprotein J (apoJ) from plasma and cerebrospinal fluid; and (ii) the interaction of sA beta with apoJ occurs in vivo as demonstrated by the ability of anti-apoeT to co-precipitate sA beta from normal cerebro spinal fluid. We have characterized the binding between A beta(1-40) and apoJ and found that the interaction is saturable, specific, and reversible. The dissociation constant of 2 x 10(-9) IM is indicative of high affinity binding. The stoichiometry of the reaction is 1:1; apoJ has five times more affinity for fresh A beta(1-40) than for the aggregated peptide. Competitive inhibition studies carried out with apolipoprotein E (isoforms E2, E3, and E4), transthyretin, vitronectin, and alpha(1)-antichymotrypsin indicate that the complex apoJ . A beta(1-40) cannot be dissociated by any of these competitors at physiologic concentrations. The data strongly suggest that apoJ plays an important role as a carrier protein for sA beta.