AMYLOID PROBES BASED ON CONGO-RED DISTINGUISH BETWEEN FIBRILS COMPRISING DIFFERENT PEPTIDES

Background: Amyloid plaques, which characterize degenerating tissue in Alzheimer's disease (brain) and type II diabetes (pancreas), were fir st visualized by staining with the dye Congo Red (CR), The ability of CR to recognize amyloid fibrils comprising diverse proteins suggests t hat the binding site includes an unidentified structural feature commo n to all amyloid fibrils. We set out to design and synthesize analogs of CR that could distinguish between fibrils comprising different pept ides, Results: Relative affinities of several CR analogs for two model amyloid fibrils were measured and compared to that of CR. Amyloid fib rils comprising peptides based on the critical carboxyl terminus of th e Alzheimer's disease amyloid protein beta 1-42 (beta 34-42) and the c ritical region of the type II diabetes pancreatic amyloid protein, IAP P (IAPP20-29) were tested. The ratio of affinities of each individual CR analog for the two amyloid fibrils varied considerably, Complexatio n of certain metal ions (Cu(II), Zn(II), Ni(II), Cd(II)) by a CR analo g did not abolish its affinity for amyloid but changed the affinity ra tio significantly. Conclusions: This study demonstrates that small org anic and organometallic molecules are capable of detecting differences in amyloid fibril structure and/or amyloid protein sequence, Molecule s of this type could have utility as neuropathological probes or imagi ng agents, since they are much easier to prepare and functionalize tha n antibodies and are specific for the fibrillar form of the amyloid pr oteins.