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.

Human tissue research in the genomic era of medicine: balancing individual and societal interests.

Advances in DNA sequencing technology and in our understanding of the human genome are ushering in a new era of genomic medicine, one with dramatic potential to not only benefit society through research involving human tissue, but also to cause economic or psychosocial harms to tissue donors and their families. This delicate situation requires that the needs of tissue donors be carefully considered and balanced with those of the medical research community, especially on issues concerning confidentiality, consent, and compensation. We analyzed the tensions between tissue donors and researchers over the research use of human tissue. We also reviewed several approaches, including the establishment of tissue-trustee infrastructures at academic medical centers, aimed at achieving a more equitable balance between individual donor protection and societal benefits derived from tissue-based research. Arch Intern Med. 2000;160:3377-3384.

Structural model for the beta-amyloid fibril based on interstrand alignment of an antiparallel-sheet comprising a C-terminal peptide.

Amyloids are a class of noncrystalline, yet ordered, protein aggregates. A new approach was used to provide the initial structural data on an amyloid fibril--comprising a peptide (beta 34-42) from the C-terminus of the beta-amyloid protein--based on measurement of intramolecular 13C-13C distances and 13C chemical shifts by solid-state 13C NMR and individual amide absorption frequencies by isotope-edited infrared spectroscopy. Intermolecular orientation and alignment within the amyloid sheet was determined by fitting models to observed intermolecular 13C-13C couplings. Although the structural model we present is defined to relatively low resolution, it nevertheless shows a pleated antiparallel beta-sheet characterized by a specific intermolecular alignment.