The communication between the brain, immune and vascular systems is a key contributor to the onset and progression of neurological diseases. Our research has uncovered pleiotropic roles for the blood coagulation factor fibrinogen in neuroinflammation, neurodegeneration, and inhibition of repair in a wide range of neurological diseases. Fibrin-targeting immunotherapy inhibits autoimmunity-and amyloid-driven neurotoxicity in animal models of multiple sclerosis, Alzheimer’s disease and COVID-19 neuropathology. Selective fibrin targeting might be beneficial for suppressing vascular-driven neurodegeneration.