The hierarchical fibril structure is explained schematically in Fig. 6. Three bi-lobed density units assemble into an extended crescent shape. Pairs of these crescent-shaped elements join back to back to form one layer of the fibril structure. Many copies of this assembly stack to form the slowly twisting helical fibril, in which columns of the globular building blocks constitute the six protofilaments of the fibril. In contrast to the generally accepted notion of a continuous cross-β core in amyloid fibrils,4,6 the globular substructure of these protofilaments gives them the appearance of a string of bi-lobed beads. The polarity of the half-fibrils arises from asymmetric connections between the protofilaments in the crescents.