The blood-brain 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. The BBB protects neurons from factors present in the systemic circulation and maintains the highly regulated CNS internal milieu, which is required for proper synaptic and neuronal functioning. BBB disruption allows influx of neurotoxic blood-derived debris, cells and microbial pathogens into the brain and is associated with inflammatory and immune responses, which can initiate multiple pathways of neurodegeneration.

This review by Sweeney and colleagues discusses the results of neuroimaging as well as biomarker studies demonstrating BBB breakdown in Alzheimer disease, Parkinson disease, Huntington disease, amyotrophic lateral sclerosis, multiple sclerosis, HIV-1-associated dementia and chronic traumatic encephalopathy. The mechanisms by which BBB breakdown leads to neuronal dysfunction and neurodegeneration are described. The importance of the BBB for therapeutic drug delivery and the adverse effects of BBB breakdown are noted, as well as opportunities to control the course of neurological diseases by targeting the BBB.

Sweeney MD, Sagare AP, Zlokovic BV: Blood-brain barrier breakdown in Alzheimer disease and neurodegenerative disorders. Nature Rev. Neurol. 14(3): 133-150 (2018).

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