The blood-brain barrier (BBB) is highly specialized to protect the brain from harmful circulating factors in the blood and maintain brain homeostasis. However, during aging and neurodegenerative disease, the BBB undergoes numerous molecular changes that can promote inflammation and disease pathogenesis. In this work, we profile the luminal (blood-facing) surface of the cerebral vasculature using sulfo-NHS-biotin to tag and enrich proteins from acutely isolate microvessedls from young (3-month-old) and aged (21-month-old) mice.