Blood-brain barrier (BBB) and aging

The blood-brain barrier (BBB) is a tightly controlled wall between your bloodstream and your brain. It is built from specialized endothelial cells lining the brain's capillaries, sealed with tight-junction proteins, and wrapped by astrocyte 'endfeet' and pericytes (cells that hug the capillaries and control leakiness). Together these form the 'neurovascular unit'. It decides what crosses between blood and brain, keeps ions balanced, and keeps out pathogens and blood-borne toxins. As you age, the barrier slowly breaks down. Pericytes are lost, tight-junction proteins drop, and the endothelium falters, so the wall gets leaky and lets blood proteins like albumin and fibrinogen seep into brain tissue. A human MRI study by Montagne et al. (2015, Neuron) showed this leakiness starts early in normal aging in the hippocampus, the memory hub, and worsens in step with mild cognitive impairment. The matching biomarker was pericyte injury (a rise in spinal-fluid PDGFR-β). A 2024 review (Cao et al., Journal of Cerebral Blood Flow & Metabolism) catalogs these changes and concludes that oxidative-stress-driven pericyte death and neuroinflammation are the most consistent drivers, though firm human proof is still limited to biomarker links, not intervention trials.

Last reviewed: June 22, 2026

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