title: Characterization of apolipoprotein J-Alzheimer's A beta interaction.
abstract: 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-apoJ to co-precipitate sA beta from normal cerebrospinal 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) M 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.
authors.affiliation: Department of Pathology, New York University Medical Center, New York 10016, USA.
authors.forename: E
authors.initials: E
authors.lastname: Matsubara
authors.forename: B
authors.initials: B
authors.lastname: Frangione
authors.forename: J
authors.initials: J
authors.lastname: Ghiso
mesh_terms: D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D001667:Binding, Competitive; D051152:Clusterin; D003169:Complement Inactivator Proteins / Q000737:chemistry / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D006023:Glycoproteins / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D007700:Kinetics; D018832:Molecular Chaperones; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry; D011485:Protein Binding
chemical_list: D016229:Amyloid beta-Peptides; C495242:CLU protein, human; D051152:Clusterin; D003169:Complement Inactivator Proteins; D006023:Glycoproteins; D018832:Molecular Chaperones; D010455:Peptides