Blood–brain barrier breakdown in Alzheimer’s disease and other neurodegenerative disorders

By Melanie D. Sweeney, A. Sagare, Berislav Zlokovic. Nature Reviews Neurology, 2018

2,586 citations recorded by the source corpus.

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 into the brain of neurotoxic blood-derived debris, cells and microbial pathogens and is associated with inflammatory and immune responses, which can initiate multiple pathways of neurodegeneration. This Review discusses neuroimaging studies in the living human brain and post-mortem tissue 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 pathogenic mechanisms by which BBB breakdown leads to neuronal injury, synaptic dysfunction, loss of neuronal connectivity and neurodegeneration are described. The importance of a healthy BBB for therapeutic drug delivery and the adverse effects of disease-initiated, pathological BBB breakdown in relation to brain delivery of neuropharmaceuticals are briefly discussed. Finally, future directions, gaps in the field and opportunities to control the course of neurological diseases by targeting the BBB are presented.

Subfields: Neurology, Physiology

View Paper: https://www.semanticscholar.org/paper/4d92c092b2819e1ed90219e4dbb45c7fe3d87806

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Citations in the corpus

Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020, background): “Decreased cerebral blood flow, coupled with increased Aβ levels induced by BBB deterioration can also aggravate tau pathology [628, 629].”
The blood–brain barrier: Structure, regulation and drug delivery (2023, background): “…to each process of the drug transportation, which have also been accompanied by reviews of latest progress in this ﬁ eld, but most of literature emphasize the BBB breakdown in speci ﬁ c brain disorders, 11 – 14 or give a general review of delivery strategies concentrating on the barrier physiology.”
Amyloid β-based therapy for Alzheimer’s disease: challenges, successes and future (2023, background): “It has been identified that the expressions of the two blood efflux transporters LRP1 and ABCB1 were reduced during AD, whereas the expression of the blood influx transporter RAGE is elevated.(21,25) The perivascular drainage pathway plays a vital role in ISF bulk-flow clearance of Aβ.”
Extracellular miRNAs: From Biomarkers to Mediators of Physiology and Disease (2019, background): “Neurodegenerative diseases which alter BBB permeability could facilitate the exchange of circulating miRNAs from the brain to the blood and vice-versa [reviewed in (Sweeney et al., 2018)].”
Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023, background): “199 Fibrinogen leaked from the site of cerebrovascular damage into the brain and subsequently bound to the receptor CD11b on the surface of microglia.”
Vascular dysfunction – the disregarded partner of Alzheimer’s disease (2019, positive): “Cerebral microbleeds are related to vascular wall damage by arteriosclerosis or CAA and also reflect a marker of ischemic white matter disease [3].”