Alzheimer's amyloid fibrils: structure and assembly.
Structural studies of Alzheimer's amyloid fibrils have revealed information about the structure at different levels. The amyloid-beta peptide has been examined in various solvents and conditions and this has led to a model by which a conformational switching occurs from alpha-helix or random coil, to a beta-sheet structure. Amyloid fibril assembly proceeds by a nucleation dependent pathway leading to elongation of the fibrils. Along this pathway small oligomeric intermediates and short fibrillar structures (protofibrils) have been observed. In cross-section the fibril appears to be composed of several subfibrils or protofilaments. Each of these protofilaments is composed of beta-sheet structure in which hydrogen bonding occurs along the length of the fibre and the beta-strands run perpendicular to the fibre axis. This hierarchy of structure is discussed in this review.
Serpell
L C
LC
Neurobiology Division, MRC Centre, Cambridge, UK. serpell@mrc-lmb.cam.ac.uk
D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D003224:Congo Red; D006801:Humans; D018625:Microscopy, Atomic Force; D015394:Molecular Structure; D009474:Neurons / Q000473:pathology; D010446:Peptide Fragments / Q000737:chemistry; D058225:Plaque, Amyloid / Q000737:chemistry; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012995:Solubility; D014961:X-Ray Diffraction
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C410220:amyloid beta-protein (11-25); D003224:Congo Red