Obesity and Alzheimer’s: An attempt to decipher the role of obesity in blood–brain barrier degradation

Abstract

The effects of obesity on memory and cognitive function have been reported, which could further lead to Alzheimer’s disease (AD). Observational studies have found both a negative and a positive association between body shape and AD. For this purpose, we designed a diffusive obesity–Alzheimer’s model consisting of fat cells, glucose, insulin, beta cells, cytokines, microglia, Aβ plaques, and neurofibrillary tangles. We have shown the developed model’s global existence, non-negativity, and long-term behavior. Additionally, equilibrium points for the ODE are analyzed for existence and stability. We adopted the Partial Rank Correlation Coefficient (PRCC) to conduct a global sensitivity analysis to estimate the most sensitive parameters responsible for Aβ and τ plaque progression. We provided a complete numerical analysis based on our deterministic and diffusive models. A patchy pattern is typically formed in mathematical simulations of spatially explicit systems, reflecting complicated spatiotemporal dynamics. This work suggests that insulin resistance and pro-inflammatory microglia may be responsible for obesity-associated cognitive decline.