Physics

Pathology

Kinetics

Monomer

Organic chemistry

Disease

Amyloid disease

Amyloid β

Biology

Biophysics

Protein aggregation

Inorganic chemistry

Chemistry

Fibril

Amyloid (mycology)

Oligomer

Amyloid fibril

Quantum mechanics

Polymer

Biochemistry

Medicine

Proceedings of the National Academy of Sciences

Significance Protein oligomers are a fundamental component of amyloidogenic disorders such as Alzheimer’s disease, being both critical intermediates in the formation of amyloid fibrils and the most toxic species on the protein aggregation pathway. Here, we derive general analytical expressions for the chemical kinetics of the oligomers generated during amyloid-formation reactions and explain how these may be used to categorize oligomers according to their basic physicochemical properties. By applying this framework to experimental kinetic data on the aggregation of a wide range of amyloidogenic proteins, we are able to determine features common to all amyloid oligomers. In particular, most are not capable of rapid growth by monomer addition, and most dissociate rather than mature into fibrils.

Kinetic diversity of amyloid oligomers