Updated project metadata. Blood-brain barrier (BBB) critically regulate the homeostasis of central nervous system (CNS). This barrier property allows cerebral vessels to meet the extremely high metabolic demand of neural activities and meanwhile protect sensitive neurons from toxic plasma components, blood immune cells and xenobiotics. Therefore, a comprehensive inventory of the molecular determinants of BBB would substantially facilitate understanding of the pathogenesis of neurological disorders involving BBB dysfunction and promote development of novel CNS drug delivery strategies. Here, we established the proteome activity landscapes of adult mouse brain, lung and liver ECs. In this study, we produced a comprehensive molecular atlas of adult mouse BBB and revealed novel insights into adult BBB in health and Alzheimer’s disease.