Stability and bifurcation analysis of Alzheimer's disease model with diffusion and three delays

A reaction-diffusion Alzheimer's disease model with three delays, which describes the interaction of β-amyloid deposition, pathologic tau, and neurodegeneration biomarkers, is investigated. The existence of delays promotes the model to display rich dynamics. Specifically, the conditions for stability of equilibrium and periodic oscillation behaviors generated by Hopf bifurcations can be deduced when delay σ (σ=σ1+σ2) or σ3 is selected as a bifurcation parameter. In addition, when delay σ and σ3 are selected as bifurcation parameters, the stability switching curves and the stable region are obtained by using an algebraic method, and the conditions for the existence of Hopf bifurcations can also be derived. The effects of time delays, diffusion, and treatment on biomarkers are discussed via numerical simulations. Furthermore, sensitivity analysis at multiple time points is drawn, indicating that different targeted therapies should be taken at different stages of development, which has certain guiding significance for the treatment of Alzheimer's disease.