Conformational change of the monomer, perhaps with several possible abnormal conformations, initiates the aggregation process. Aggregation (see Box 2 for definitions) begins as soon as there is an association of two or more abnormal proteins or parts of proteins. Amyloid fibrils might be formed by the linear addition of monomers to the growing fibre (arrows on right), or through intermediate oligomeric assemblies, or species called protofibrils, either of which might be 'off' the pathway to fibril formation. Oligomers or protofibrils might be capable of forming annular rings. Furthermore, amorphous aggregates, which do not contain fibrils, can also be formed, possibly through the oligomeric or protofibrillar intermediates as shown, or through precipitation of monomers (not shown). If an aggregate becomes large enough, it can be visualized by light microscopy, and large well-demarcated aggregates in cells are often termed inclusion bodies. It is currently proposed that the early species in the aggregation process are more toxic than inclusion bodies or large aggregates. Further research is needed to clarify these pathways, determine similarities and differences between the pathways for different diseases and determine the points where inhibition might be beneficial or detrimental for the disease process. Molecular components are not drawn to scale.