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 first visualized by staining with the dye Congo Red (CR). The ability of CR to recognize amyloid fibrils comprising diverse proteins suggests that the binding site includes an unidentified structural feature common to all amyloid fibrils. We set out to design and synthesize analogs of CR that could distinguish between fibrils comprising different peptides.


RESULTS
Relative affinities of several CR analogs for two model amyloid fibrils were measured and compared to that of CR. Amyloid fibrils comprising peptides based on the critical carboxyl terminus of the Alzheimer's disease amyloid protein beta1-42 (beta34-42) and the critical region of the type II diabetes pancreatic amyloid protein, IAPP (IAPP20-29) were tested. The ratio of affinities of each individual CR analog for the two amyloid fibrils varied considerably. Complexation of certain metal ions (Cu(II), Zn(II), Ni(II), Cd(II)) by a CR analog did not abolish its affinity for amyloid but changed the affinity ratio significantly.


CONCLUSIONS
This study demonstrates that small organic and organometallic molecules are capable of detecting differences in amyloid fibril structure and/or amyloid protein sequence. Molecules of this type could have utility as neuropathological probes or imaging agents, since they are much easier to prepare and functionalize than antibodies and are specific for the fibrillar form of the amyloid proteins.
Ashburn
T T
TT
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. ptljr@mit.edu
Han
H
H
McGuinness
B F
BF
Lansbury
P T
PT
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D003224:Congo Red; D009682:Magnetic Resonance Spectroscopy; D015335:Molecular Probes; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*
D016229:Amyloid beta-Peptides; D015335:Molecular Probes; D010455:Peptides; D003224:Congo Red