The Interaction Between Tau and Microglia-induced Neuroinflammation as a Cause of Alzheimer's Disease: A Computational Study
Sai Yashasvi Kasthala
21/07/2026
Alzheimer’s disease (AD) is a neurodegenerative disease that is characterized by gradual cognitive decline, memory loss, and neuronal death. Physically, AD is marked by amyloid-beta plaques, tau pathology, and neuroinflammation. While these processes, especially amyloid-beta, are usually studied independently, emerging evidence suggests they interact in a feedback loop that accelerates disease progression. This study aims to explore the impact of microglial activation on the rate of tau aggregation and propagation in Alzheimer’s disease. A computational approach using Complex Pathway Simulator (COPASI) was implemented, using both a full brain model and a regional model with multiple, interconnected compartments representing Braak regions. Microglia activation levels were varied across three conditions (low, medium, high) and tau accumulation, propagation, and aggregation dynamics were examined. Results showed that increased microglial activation increased tau exposure, accelerated aggregation, and reduced the time to peak aggregation rate. However, final tau burden remained relatively stable, which could be attributed to system saturation. In the regional model, higher activation led to an increased impact in later Braak stages, and Braak staging was preserved throughout the simulation. These findings support the idea that neuroinflammation amplifies tau pathology through a positive feedback loop. It is also possible that microglial activation primarily impacts the rate of the processes rather than the magnitude of the processes themselves. This study highlights the importance of computational modeling in isolating variables, such that causal inferences may be drawn, and suggests that early, anti-inflammatory interventions may be critical for slowing disease progression.