Blood–brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders
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TLDR
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.Abstract:
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 presentedread more
Citations
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Journal ArticleDOI
Blood-Brain Barrier: From Physiology to Disease and Back
TL;DR: This review examines molecular and cellular mechanisms underlying the establishment of the blood-brain barrier, and examines how BBB dysfunction relates to neurological deficits and other pathologies in the majority of sporadic AD, PD, and ALS cases, multiple sclerosis, other neurodegenerative disorders, and acute CNS disorders.
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Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here?
Fangda Leng,Paul Edison +1 more
TL;DR: The interrelationships between Neuroinflammation and amyloid and tau pathologies as well as the effect of neuroinflammation on the disease trajectory in AD are discussed, focusing on microglia as major players in neuro inflammation and how these cells could be modulated as a therapeutic strategy for AD.
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Blood-brain barrier breakdown is an early biomarker of human cognitive dysfunction.
Daniel A. Nation,Melanie D. Sweeney,Axel Montagne,Abhay P. Sagare,Lina M. D'Orazio,Maricarmen Pachicano,Farshid Sepehrband,Amy R. Nelson,David P. Buennagel,Michael G. Harrington,Tammie L.S. Benzinger,Anne M. Fagan,John M. Ringman,Lon S. Schneider,John C. Morris,Helena C. Chui,Meng Law,Arthur W. Toga,Berislav V. Zlokovic +18 more
TL;DR: Neuroimaging and cerebrospinal fluid analyses in humans reveal that loss of blood–brain barrier integrity and brain capillary pericyte damage are early biomarkers of cognitive impairment that occur independently of changes in amyloid-β and tau.
Journal ArticleDOI
Single-Cell Transcriptome Atlas of Murine Endothelial Cells
Joanna Kalucka,Laura P.M.H. de Rooij,Jermaine Goveia,Katerina Rohlenova,Sébastien J. Dumas,Elda Meta,Nadine V. Conchinha,Federico Taverna,Laure-Anne Teuwen,Koen Veys,Melissa García-Caballero,Shawez Khan,Vincent Geldhof,Liliana Sokol,Rongyuan Chen,Lucas Treps,Mila Borri,Pauline de Zeeuw,Charlotte Dubois,Tobias K. Karakach,Kim D. Falkenberg,Magdalena Parys,Xiangke Yin,Stefan Vinckier,Yuxiang Du,Robert A. Fenton,Luc Schoonjans,Luc Schoonjans,Mieke Dewerchin,Guy Eelen,Bernard Thienpont,Lin Lin,Lars Bolund,Xuri Li,Yonglun Luo,Peter Carmeliet,Peter Carmeliet +36 more
TL;DR: An atlas of >32,000 single-EC transcriptomes from 11 mouse tissues was constructed and 78 EC subclusters were identified, including Aqp7+ intestinal capillaries and angiogenic ECs in healthy tissues and provides a powerful discovery tool and resource value.
Journal ArticleDOI
APOE4 leads to blood–brain barrier dysfunction predicting cognitive decline
Axel Montagne,Daniel A. Nation,Abhay P. Sagare,Giuseppe Barisano,Melanie D. Sweeney,Ararat Chakhoyan,Maricarmen Pachicano,Elizabeth Joe,Amy R. Nelson,Lina M. D'Orazio,David P. Buennagel,Michael G. Harrington,Tammie L.S. Benzinger,Anne M. Fagan,John M. Ringman,Lon S. Schneider,John C. Morris,Eric M. Reiman,Richard J. Caselli,Helena C. Chui,Julia Tcw,Yining Chen,Judy Pa,Peter S. Conti,Meng Law,Meng Law,Arthur W. Toga,Berislav V. Zlokovic +27 more
TL;DR: The findings suggest that breakdown of the BBB contributes to APOE4-associated cognitive decline independently of Alzheimer’s disease pathology, and might be a therapeutic target inAPOE4 carriers.
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