Nox2 has emerged as an important redox enzyme in hypertension,9,10,38 Alzheimer’s disease-like amyloid pathology13,14 and ageing.8,39 Here, we demonstrate that Nox2 underpins pivotal mechanisms of cerebrovascular injury such as microvascular inflammation and neurovascular dysfunction, which ultimately contribute to white matter pathology and cognitive impairment in an experimental model relevant to VCI. This evidence concerns the gene CYBB and hypertensive disorder.