These data indicate that the contribution of systemic infection to brain cytokine expression and vascular insufficiency varies according to disease stage: cerebral hypoperfusion and blood–brain barrier is exacerbated by infection and is related to elevated brain cytokine expression at an early stage of Alzheimer’s disease, independently of amyloid-β, whereas pericyte loss, raised EDN1, and further blood–brain barrier breakdown, are related to amyloid-β accumulation in late-stage disease. Here, EDN1 is linked to early-onset autosomal dominant Alzheimer disease.