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The formation and proliferation of protein aggregates play a central role ina number of devastating neuro-degenerative diseases. Many experimental studiesindicate that the ability of existing aggregates to replicate is a key propertyin generating their pathogenic effect across a range of diseases. However,given the complexity of the process in vivo, no principled general approachcurrently exists to obtain the rates of the fundamental steps that underlieaggregate formation from measurements in living systems. In order to addressthis challenge, here we present a general approach for analysing aggregationkinetics that considers broad classes of processes that can be described by afamily of scaling solutions. Our approach is not limited only to fibrillaraggregates, but applies to any aggregate shape. We show that the rates canreliably be extracted by fitting of a simple logistic function, even fromexperimental data in living systems, and give a very general analyticalexpression that relates the scaling of the exponential rate with monomerconcentration to the microscopic details of the underlying reaction. Thisapproach can thus be used to infer the microscopic mechanism driving theaggregation process from macroscopic measurements in complex systems.

Mechanism, scaling and rates of protein aggregation from in vivo measurements