Alzheimer's disease: A matter of blood-brain barrier dysfunction?
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TLDR
The role of blood–brain barrier dysfunction in Alzheimer’s neurodegeneration and how targeting the BBB can influence the course of neurological disorder in transgenic models with human APP, PSEN1 and TAU mutations, APOE4 (major genetic risk), and pericyte degeneration causing loss of BBB integrity are examined.Abstract:
The blood-brain barrier (BBB) keeps neurotoxic plasma-derived components, cells, and pathogens out of the brain. An early BBB breakdown and/or dysfunction have been shown in Alzheimer's disease (AD) before dementia, neurodegeneration and/or brain atrophy occur. However, the role of BBB breakdown in neurodegenerative disorders is still not fully understood. Here, we examine BBB breakdown in animal models frequently used to study the pathophysiology of AD, including transgenic mice expressing human amyloid-β precursor protein, presenilin 1, and tau mutations, and apolipoprotein E, the strongest genetic risk factor for AD. We discuss the role of BBB breakdown and dysfunction in neurodegenerative process, pitfalls in BBB measurements, and how targeting the BBB can influence the course of neurological disorder. Finally, we comment on future approaches and models to better define, at the cellular and molecular level, the underlying mechanisms between BBB breakdown and neurodegeneration as a basis for developing new therapies for BBB repair to control neurodegeneration.read more
Citations
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Journal ArticleDOI
Blood–brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders
TL;DR: 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.
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.
Journal ArticleDOI
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
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.
Journal ArticleDOI
The role of brain vasculature in neurodegenerative disorders.
TL;DR: A hypothetical model of Alzheimer’s disease biomarkers is proposed to include brain vasculature as a factor contributing to the disease onset and progression, and a common pathway linking brain vascular contributions to neurodegeneration in multiple Neurodegenerative disorders is suggested.
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