Cortical astrocytes expressing lipoprotein receptor-related protein 4 (LRP4) form direct contacts with brain arteries and regulate laminin-α5 production in vessel basement membranes. When these specialized GFAP-negative astrocytes are depleted experimentally, cerebral blood flow decreases alongside reductions in vessel diameter, branching density, and laminin-α5 levels. The cells concentrate along the brain's outer surface (pia) rather than distributing uniformly like conventional astrocytes. This discovery adds critical nuance to our understanding of neurovascular coupling—the brain's mechanism for matching blood flow to neural activity. Previous research has focused heavily on GFAP-positive astrocytes and pericytes as primary regulators of cerebral circulation, but LRP4+ astrocytes appear to serve a specialized maintenance role for the vascular basement membrane architecture. Their loss triggers compensatory increases in conventional astrocytes and microglia, suggesting they normally help maintain tissue homeostasis. In Alzheimer's disease models, these protective astrocytes decline along brain surfaces while avoiding amyloid plaques, potentially contributing to the vascular dysfunction that precedes neurodegeneration. The findings suggest that preserving LRP4+ astrocyte populations could represent a novel therapeutic target for maintaining healthy brain circulation during aging and neurological disease.