Fig. 6

Idealised mathematical model and simulations. a: The conceptual formulation of the idealised model from known physiology. Specifically, the bone marrow produces proinflammatory cells on demand, which is triggered by some unknown exogenous signal I(t). The bone marrow can be seen as having a finite reservoir of readily available resources which enables production of proinflammatory cells m(t). The underlying law for the production of proinflammatory cells is given by the Markov state diagram and the time evolution given by the differential equation (idealised model). b: Simulations of the idealized model for two scenarios. The left-top inset panel depicts the pathological case in which an exogenous signal triggers the production of proinflammatory cells across all disease stages (SMC, MCI, AD), however due to finite resources the production saturates. The left-bottom shows that the migration capacity of monocytes decreases during the progression of the disease. The right-top inset panel depicts a rescue scenario where the exogenous signal causative of AD is identified and therapeutically targeted. In this case, proinflammatory cells and migration capacity return to healthy values.