Brain endothelial injury is a common pathology in Alzheimer disease (AD) brains. Structural changes consistent with brain endothelial injury are observed in almost all AD brains at autopsy and occur independently of other forms of vascular pathology. Emerging evidence supports an important role for the brain endothelium in mediating amyloid and tau aggregation and contributing to impaired neurogenesis and altered synaptic plasticity. Despite its importance, our understanding of the role of endothelial dysfunction in AD pathogenesis, and the mechanisms by which endothelial alterations contribute to neurodegeneration and cognitive impairment in AD, has been limited by the absence of reliable fluid markers for brain endothelial injury. Vascular endothelial-cadherin (VE-cadherin) is an abundantly expressed endothelium-specific protein that plays an important role in maintaining the blood-brain barrier. Recent studies using proteomics and transcriptomics suggest VE-cadherin may be a useful cerebrospinal fluid (CSF) marker for brain endothelial injury in AD, including the early preclinical stages, and has strong potential for use as a diagnostic, prognostic, and outcome measure in clinical studies of AD. Further research to identify and validate other biomarkers of brain endothelial injury will be important to elucidate endothelial contributions to the onset and progression of AD pathology and the onset of cognitive impairment.