A SEMA4D blocking antibody was reported to reduced astrogliosis, BBB impairment and pathology in rat models of experimental autoimmune encephalomyelitis (EAE) and produce beneficial effects on cognitive performances in the CVN mice, a disease model that reproduces many features of AD-like pathology, directinteraction with Plexin including neuroinflammation (Smith et al., 2015; Evans et al., 2022). Here, SEMA4D is linked to Alzheimer disease.