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- Title
The C-Terminus of the β Protein is Critical in Amyloidogenesis.
- Authors
JARRETT, JOSEPH T.; BERGER, ELIZABETH P.; LANSBURY, PETER T.
- Abstract
The β amyloid protein found in extracellular deposits in Alzheimer's disease (AD) is heterogeneous at its C-terminus; proteins ending at residues 40, 42, and 43 have been identified in neuritic deposits, while protein in vascular amyloid appears to end at residue 39 or 40. Studies of synthetic β proteins (β1-39, β1-40, β1-42), and model peptides (β26-39, β26-40, β26-42, β26-43) demonstrate that amyloid formation is a nucleation-dependent phenomenon. Peptides ending at residues 39 or 40 were kinetically soluble for hours to days, while peptides ending at residues 42 or 43 aggregated immediately; all eventually reached similar thermodynamic solubility. The kinetically soluble variants could be seeded with the kinetically insoluble variants. The secondary structure of β26-39 fibrils was different from that of β26-42 fibrils, however, seeding β26-39 with β26-42 produces mixed fibrils with structure similar to β26-42. These results suggest that neuritic plaques may be seeded by their minor component; this may determine the structure and properties of amyloid in AD.
- Publication
Annals of the New York Academy of Sciences, 1993, Vol 695, Issue 1, p144
- ISSN
0077-8923
- Publication type
Article
- DOI
10.1111/j.1749-6632.1993.tb23043.x