TLR4 and Alzheimer disease: We emphasize its utility in resolving causality, identifying conserved cytokine pathways, and modeling systemic inflammation relevant to Parkinson's and Alzheimer's disease.<h4>Key findings</h4><i>Drosophila</i> possesses a tripartite immune system that is brain-resident glia, circulating hemocytes, and the fat body that coordinates responses via Toll, Immune deficiency (Imd), JAK/STAT, and MAPK pathways.