Figure 1

Schematic representation of the kinetics of cell loss predicted by a cumulative-damage model. (A) Ratio of intact neurons (N(t)/N₀) as a function of time t shows a sigmoidal shape in the cumulative damage model (Eq. 2 and 3). (B) When displayed on a semi-log graph, neuronal survival curves over time, producing a shoulder shape. (C-E) PolyQ-length dependence of neuronal cell loss by the cumulative damage model. (C) Assuming that the extent of neuronal cell loss at the onset of disease is identical irrespective of polyQ-length (red line: 30% cell loss is defined as symptom onset), the relationship between polyQ-length and age-of-onset shows a sigmoidal function (Eq. 5b), and then the time course of neuronal cell loss for each polyQ-length should be described by sigmoidal kinetics, [as the disease proceeds, t(0.7) → t(0.3)]. (D) Relationship between polyQ-length and age at an identical ratio of cell loss for each polyQ-length shows a sigmoidal shape. Red line: age at onset for each polyQ-length [30% neuronal loss, t(0.7)]. (E) Semi-log plots of polyQ-length versus age at an identical ratio of cell loss for each polyQ-length show that the risks of cell death are represented by the correlation between polyQ-length and age-of-onset (red line).