Blood-brain barrier (BBB) and aging

The blood-brain barrier (BBB) is a highly selective neurovascular interface formed by specialised endothelial cells lining cerebral capillaries, reinforced by tight-junction proteins, astrocytic endfeet, and pericytes (mural cells that wrap around capillary walls and regulate permeability). Together these elements constitute the neurovascular unit, which controls the passage of molecules between blood and brain parenchyma, maintains ion homeostasis, and excludes pathogens and blood-derived neurotoxins. With advancing age the BBB undergoes progressive structural and functional deterioration: pericyte loss, reduced tight-junction protein expression, and endothelial dysfunction increase paracellular permeability, allowing albumin, fibrinogen, and other plasma proteins to leak into the neuropil. A human imaging study by Montagne et al. (2015, Neuron) using dynamic contrast-enhanced MRI demonstrated that BBB breakdown in the hippocampus — a region central to episodic memory — occurs early in normal aging and worsens in proportion to the degree of mild cognitive impairment, with pericyte injury (indexed by elevated cerebrospinal-fluid PDGFR-β) as the correlating biomarker. A 2024 review in the Journal of Cerebral Blood Flow & Metabolism (Cao et al.) catalogues age-related BBB changes across all cellular components and concludes that oxidative-stress-driven pericyte apoptosis and neuroinflammatory signalling are the most mechanistically consistent drivers identified across human and rodent data, though direct causal evidence in humans remains limited to biomarker associations rather than intervention studies.