Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders

By Berislav Zlokovic. Nature Reviews Neuroscience, 2011

2,807 citations recorded by the source corpus.

The neurovascular unit (NVU) comprises brain endothelial cells, pericytes or vascular smooth muscle cells, glia and neurons. The NVU controls blood–brain barrier (BBB) permeability and cerebral blood flow, and maintains the chemical composition of the neuronal 'milieu', which is required for proper functioning of neuronal circuits. Recent evidence indicates that BBB dysfunction is associated with the accumulation of several vasculotoxic and neurotoxic molecules within brain parenchyma, a reduction in cerebral blood flow, and hypoxia. Together, these vascular-derived insults might initiate and/or contribute to neuronal degeneration. This article examines mechanisms of BBB dysfunction in neurodegenerative disorders, notably Alzheimer's disease, and highlights therapeutic opportunities relating to these neurovascular deficits.

Subfields: Neurology, Physiology

View Paper: https://www.semanticscholar.org/paper/4fa8886bfa6c3a8c6eaf72b32c063e6273ef9107

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Citations in the corpus

Nanoparticle-mediated brain drug delivery: Overcoming blood-brain barrier to treat neurodegenerative diseases. (2016, background): “In other cases, especially in chronic neurodegenerative conditions like AD and PD, it remains unclear if it is a downstream process or if it plays a role in disease onset and development [74,75].”
Brain metabolism in health, aging, and neurodegeneration (2017, positive): “Considerable evidence suggests that the BBB integrity is compromised in AD patients (Glenner, 1979, 1985; Powers et al, 1981; Zipser et al, 2007; Zlokovic, 2011).”
The pathobiology of vascular dementia (2013, positive): “…a previously unrecognized functional and pathogenic synergy between neurons, glia, and vascular cells (Iadecola, 2010; Quaegebeur et al., 2011; Zlokovic, 2011), providing a new framework to reevaluate how alterations in cerebral blood vessels could contribute to the neuronal dysfunction…”
A blood–brain barrier overview on structure, function, impairment, and biomarkers of integrity (2020, background): “Abbreviations BBB: Blood–brain barrier; CNS: Central nervous system; CSF: Cerebrospinal fluid; BCB: Blood–CSF barrier; ISF: Interstitial fluid; TJs: Tight junctions; P-gp: P-glycoprotein; BCRP: Breast cancer resistance protein; OATP: Organic anion transporting polypeptide; CYP 450: Cytochrome P450; ”
In vitro models of the blood–brain barrier: An overview of commonly used brain endothelial cell culture models and guidelines for their use (2016, background): “The BBB changes properties during Alzheimer’s disease, which contributes to- and may even be a leading cause of neurodegeneration.(294,295) In vitro BBB models have been extensively applied to investigate changes caused by the Alzheimer’s disease environment and to investigate the ability of the BBB”
Blood-Brain Barrier Breakdown in the Aging Human Hippocampus (2015, positive): “Although, our CSF biomarkers analysis did not show endothelial cell injury, involvement of inflammatory cytokines, and/or direct vasculotoxic effects of Ab in MCI, it is possible that some of these factors could play a role in magnifying BBB damage at later disease stages during progression to demen”
The Epidemiology of Alzheimer's Disease Modifiable Risk Factors and Prevention (2021, background): “Neurovascular unit disorder, due to cerebrovascular diseases, could cause decreased cerebral blood flow, induce blood-brain barrier disruptions as well as selective brain atrophies, all of which could result in direct damage to neurons and trigger Aβ accumulation indirectly (56).”
Neuroinflammation in Alzheimer's disease: Current evidence and future directions (2016, background): “Moreover, brain microvessels from AD subjects secrete higher amounts of cytokines, which can contribute to neuronal damage [11].”
The overlap between vascular disease and Alzheimer’s disease - lessons from pathology (2014, background): “CVD has been suggested to contribute to AD neuropathological changes including selective brain atrophy and accumulation of abnormal proteins such as Aβ [24,35,84,85].”
The Glymphatic System – A Beginner's Guide (2015, neutral): “At the cortical surface, cerebral arteries extend into pial arteries running through the CSF-containing subarachnoid space and the subpial space [44, 45].”
Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020, background): “The BBB prevents neurotoxic plasma components, pathogens, and blood cells from entering the brain, and regulates the molecular transport of components into and out of the CNS to homeostatically regulate the neuronal extracellular environment [623, 624].”
Ageing as a risk factor for disease. (2012, background): “Neurodegeneration Nutrient-sensing pathways act indirectly via cardiovascular disease to affect AD because the risk of AD is related to cardiovascular disease risk profile, and AD may indeed have a strong vascular component [39].”
Pericytes of the neurovascular unit: Key functions and signaling pathways (2016, background): “(b) Under physiological conditions (top row), pericytes regulate (1) BBB integrity, i.”