The Mechanism Underlying Amyloid Polymorphism is Opened for Alzheimer's Disease Amyloid-β Peptide

It has been demonstrated using A beta(40) and A beta(42) recombinant and synthetic peptides that their fibrils are formed of complete oligomer ring structures. Such ring structures have a diameter of about 8-9 nm, an oligomer height of about 2-4 nm, and an internal diameter of the ring of about 3-4 nm. Oligomers associate in a fibril in such a way that they interact with each other, overlapping slightly. There are differences in the packing of oligomers in fibrils of recombinant and synthetic A beta peptides. The principal difference is in the degree of orderliness of ring-like oligomers that leads to generation of morphologically different fibrils. Most ordered association of ring-like structured oligomers is observed for a recombinant A beta(40) peptide. Less ordered fibrils are observed with the synthetic A beta(42) peptide. Fragments of fibrils the most protected from the action of proteases have been determined by tandem mass spectrometry. It was shown that unlike A beta(40), fibrils of A beta(42) are more protected, showing less ordered organization compared to that of A beta(40) fibrils. Thus, the mass spectrometry data agree with the electron microscopy data and structural models presented here.