Investigating Potential Alzheimer's Disease Therapies through an Agent-Based Model of Impaired Microglia MetabolismModeling Impaired Microglia Metabolism

Alzheimer’s disease is the leading cause of dementia globally and is marked by amyloid-β plaque accumulation, decreased brain pH, disrupted metabolism, and increased permeability of the blood-brain barrier. Microglia, the resident immune cells of the central nervous system, are essential for maintaining brain homeostasis and are critically involved in the progression of AD. While microglia can initiate protective immune responses to injury and disease, dysregulated microglial metabolism may contribute to the exacerbation of Alzheimer's pathology. To investigate potential therapeutic strategies, we developed an agent-based model simulating the effects of exercise and metabolic enhancement on dysfunctional microglia. Our findings suggest that these interventions can reduce amyloid-β plaque accumulation and slow the blood brain barrier breakdown; however, they may also unintentionally lower brain pH, highlighting a trade-off that warrants further investigation.