Figure 1

Validity of the model using in vitro data and clinical data. (A) The model was validated using in vitro data. It is impossible to experimentally determine the aggregation kinetics for polyQ peptides at physiological concentrations. However, assuming no change in mechanism, Chen et al, calculated the aggregation kinetics at low concentration (0.1 nM) from data obtained from aggregation of polyQ peptides at high concentration using the kinetics parameters of Equation 1 [9]. We tested the linear correlation of the natural log transform of these data, which represents the time required for 0.9% aggregation of polyQ peptides, against the polyQ tract number. A simple logarithmic transformation of the aggregation lag times did not show a linear relationship. In contrast, using t _E ² = 27 in our model, nucleation lag times perfectly matched a linear relation. (B) A linear regression analysis of natural log-transformed age-of-onset versus CAG size in SCA1 patients revealed that the plots of residual error versus CAG size were better fit to a U-shaped curve.