FIG. 3.

Using the AND model as a simulator for hypothesis generation. In this example, we explore how the brain-wide total tangle burden would depend on the rate of monomer production in the initial seed region (here, entorhinal cortex), and whether tangle burden would be rate-limited by network transmissibility. (A) Evolution of total tangle burden ${\Sigma }_i{\tau }_M\left(i,t\right)$ over model time t, for various levels of the rate of monomer production. Clearly, higher production rates yield higher τ burden. (B) Maximum τ burden against production rate, indicating a strong sub-linear relationship. Three curves represent different transmissibility regimes, governed by parameter $\beta$: low, mid, and high. Tangle burden is limited at low transmissibility, and almost linear against production rate at high transmissibility. (C) Model time at which the peak tangle burden was achieved, versus production rate, indicating an inverse relationship between tangle growth duration and both monomer production rate and network transmissibility. Color images are available online.