CONGO RED INHIBITS PROTEOGLYCAN AND SERUM AMYLOID-P BINDING TO AMYLOID-BETA FIBRILS

Various data suggest that Alzheimer's disease results from the accumul ation of amyloid beta (A beta) peptide fibrils and the consequent form ation of senile plaques in the cognitive regions of the brain. One app roach to lowering senile plaque burden in Alzheimer's disease brain is to identify compounds that will increase the degradation of existing amyloid fibrils. Previous studies have shown that proteoglycans and se rum amyloid P (SAP), molecules that localize to senile plaques, bind t o A beta fibrils and protect the amyloid peptide from proteolytic brea kdown. Therefore, molecules that prevent the binding of SAP and/or pro teoglycans to fibrillar A beta might increase plaque degradation and p rove useful in the treatment of Alzheimer's disease. The nature of SAP and proteoglycan binding to A beta is defined further in the present study. SAP binds to both fibrillar and nonfibrillar forms of A beta. H owever, only the for;mer is rendered resistant to proteolysis after SA P association. It is interesting that both SAP and proteoglycan bindin g to A beta fibrils can be inhibited by glycosaminoglycans and Congo r ed. Unexpectedly, Congo red protects fibrillar A beta from breakdown, suggesting that this compound and other structurally related molecules are unlikely to be suitable for use in the treatment of Alzheimer's d isease.