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Key Points The bloodbrain barrier (BBB) protects neurons from factors present in the systemic circulation and maintains the highly regulated brain internal milieu, which is required for proper synaptic and neuronal functioning BBB breakdown facilitates entry into the brain of neurotoxic blood-derived products, cells and pathogens and is associated with inflammatory and immune responses, which can initiate multiple neurodegenerative pathways Neuroimaging studies have demonstrated early BBB dysfunction in Alzheimer disease and other neurodegenerative disorders, which is also supported by biofluid biomarker data and is consistently observed in post-mortem tissue BBB dysfunction in neurodegenerative disorders includes increased BBB permeability, microbleeds, impaired glucose transport, impaired P-glycoprotein 1 function, perivascular deposits of blood-derived products, cellular infiltration and degeneration of pericytes and endothelial cells Abstract The bloodbrain barrier (BBB) is a continuous endothelial membrane within brain microvessels that has sealed cell-to-cell contacts and is sheathed by mural vascular cells and perivascular astrocyte end-feet

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