Figure 1.
Model predictions for levels of Aβ and tau under normal and AD conditions (no immunisation).
The mean curves from 100 stochastic simulations are plotted for different Aβ clearance rates. The shaded regions represent the one standard deviation from the mean. A kdegAbeta = 1.5e-5 s−1), B kdegAbeta = 2.1e-5 s−1), C kdegAbeta = 1.0e-4s−1, D kdegAbeta = 2.0e-4s−1. Key: orange = soluble Aβ; blue = Aβ plaques; green = phospho-tau; black = tau tangles; red = activated glia.
Figure 2.
Model predictions for levels of Aβ, tau, activated glia under different simulated interventions.
The mean curves from 100 stochastic simulations are plotted (six individual runs are shown in Fig. S2). The shaded regions represent the one standard deviation from the mean. A–D Simulated passive immunisation administered at different time-points: A Day 0; B Day 4; C Day 8; D Repeated immunisation at Day 0 and Day 7. E Simulated active immunisation. F No immunisation. Key: orange = soluble Aβ; blue = Aβ plaques; green = phospho-tau; black = tau tangles; red = activated glia.
Figure 3.
Model predictions for levels of ROS, Gsk3β and phospho-tau under different simulated interventions.
The mean curves from 100 stochastic simulations are plotted. A Active Gsk3β B Phospho-tau; C ROS. Key: blue = day 0; green = day 4; red = day 8; D orange = repeated immunisation at Day 0 and Day 7; black = no immunisation.
Table 1.
Summary of parameter scans showing the effect of increasing the parameter value by a factor of two on the levels of Aβ, tau, glia and ROS.
Table 2.
Parameters ranked in order of their effect on Aβ Plaques.
Table 3.
Parameters ranked in order of their effect on tangles.
Figure 4.
Cycle of reactions leading to aggregation of Aβ and tau.
Immunisation reduces aggregation of both Aβ and tau by breaking the cycle. However stress within the cell may still cause activation of p53 and GSK3β so that the aggregation process of tau continues.
Table 4.
Additional species for the immunotherapy model. All other species in the model are given in Proctor & Gray [20].
Table 5.
Additional reactions for the immunotherapy model. All other reactions in the model are given in Proctor & Gray [20].
Table 6.
Values for additional parameters in the immunotherapy model. All other parameters in the model are given in Proctor & Gray [20].