Agent-based Modeling of Microglia Behavior in the Context of Alzheimer's Disease*

Whether immune cells protect or harm the brain is an open question depending on context, and their role is implicated in multiple diseases such as Alzheimer's Disease, dementia, and other neurological disorders.  Microglia, a specific type of immune cell in the central nervous system, play a key role in homeostasis, and genes associated with an elevated risk of Alzheimer's disease correspond with deficiencies in their behavior.  We create an agent-based model that incorporates inflammatory signaling, chemotaxis, and phagocytosis of damaged neurons and allows the exploration of crucial pathways in the maintenance of brain health.  We specifically investigated pathways related to Alzheimer's risk variants of the gene TREM2 which results in impaired microglia phagocytosis and sensing.