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.
Highlights
Proteins are co-deposited with A{3 in senile plaques
Amyloid P-component, al-antichymotrypsin (ACT), apolipoprotein E, apolipoprotein J, complement components, vitronectin (Vn), glycosaminoglycans, and extracellular matrix proteins are among the amyloid-associated proteins described so far [7,8,9,10,11,12,13,14,15]
Using immobilized synthetic peptides homologous to A{3 (A{31-40)' we have shown previously its binding association with plasma and CSF apolipoproteins J and E; the presence of the complex apoJ'sA{3 was confirmed in CSF, indicating that the interaction takes place in vivo [18, 20]
Summary
Vol 270, No 13, Issue of March 31, pp. 7563-7567, 1995 Printed in U.S.A. (Received for publication, November 7, 1994, and in revised form, January 25, 1995). Whether or not sA{3 is the immediate precursor of A{3, it is clear that the same amino acid sequence can have both fibrillar and non-fibrillar conformations; the knowledge ofthe factors that influence its behavior in solution will be a step forward in the understanding of AD pathology. In this regard, the existence of specific components named "desaggrins" was previously suggested based on the fact that A{31-40 spontaneous fibril formation in vitro is inhibited in the presence of CSF [6]
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