Blood-Brain Barrier Integrity and Clearance of Amyloid-β from the BBB

Cockerill, Irsalan; Oliver, Joy-anne N.; Xu, Huaxi; Fu, Bingmei M.; Zhu, Donghui

doi:10.1007/978-3-319-96445-4_14

Cited by 48 publications

(37 citation statements)

References 23 publications

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“…A deficiency in Aβ clearance due to an impairment of the blood–brain barrier (BBB) has been associated with AD development [66]. In this way, the integrity of the BBB is important, since Aβ clearance ameliorates AD neuropathology [67].…”

Section: Lps-induced Inflammation In Models Of Alzheimer’s Diseasementioning

confidence: 99%

Lipopolysaccharide-Induced Neuroinflammation as a Bridge to Understand Neurodegeneration

Batista

Gomes

Candelario‐Jalil

et al. 2019

IJMS

384

233

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A large body of experimental evidence suggests that neuroinflammation is a key pathological event triggering and perpetuating the neurodegenerative process associated with many neurological diseases. Therefore, different stimuli, such as lipopolysaccharide (LPS), are used to model neuroinflammation associated with neurodegeneration. By acting at its receptors, LPS activates various intracellular molecules, which alter the expression of a plethora of inflammatory mediators. These factors, in turn, initiate or contribute to the development of neurodegenerative processes. Therefore, LPS is an important tool for the study of neuroinflammation associated with neurodegenerative diseases. However, the serotype, route of administration, and number of injections of this toxin induce varied pathological responses. Thus, here, we review the use of LPS in various models of neurodegeneration as well as discuss the neuroinflammatory mechanisms induced by this toxin that could underpin the pathological events linked to the neurodegenerative process.

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Section: Lps-induced Inflammation In Models Of Alzheimer’s Diseasementioning

confidence: 99%

Lipopolysaccharide-Induced Neuroinflammation as a Bridge to Understand Neurodegeneration

Batista

Gomes

Candelario‐Jalil

et al. 2019

IJMS

384

233

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“…Together, the NVU and BBB contribute to the complex process of amyloid clearance in the healthy brain. This involves several specialized transporters in the endothelial cell membrane, including LDL-family receptors and transporters for carrier proteins to which Aβ can bind like apolipoprotein J (APOJ), APOE and α2-macroglobulin [173,174,175]. Thus, vascular cells play an important physiological role in the regulation of brain Aβ levels, both in terms of actively transporting Aβ into vessels and in regulating perfusion and removal from the brain.…”

Section: Cerebrovascular Alterations In Alzheimer’s Diseasementioning

confidence: 99%

Vascular Dysfunction in Alzheimer’s Disease: A Prelude to the Pathological Process or a Consequence of It?

Govindpani

McNamara

Smith

et al. 2019

JCM

178

142

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Alzheimer’s disease (AD) is the most prevalent form of dementia. Despite decades of research following several theoretical and clinical lines, all existing treatments for the disorder are purely symptomatic. AD research has traditionally been focused on neuronal and glial dysfunction. Although there is a wealth of evidence pointing to a significant vascular component in the disease, this angle has been relatively poorly explored. In this review, we consider the various aspects of vascular dysfunction in AD, which has a significant impact on brain metabolism and homeostasis and the clearance of β-amyloid and other toxic metabolites. This may potentially precede the onset of the hallmark pathophysiological and cognitive symptoms of the disease. Pathological changes in vessel haemodynamics, angiogenesis, vascular cell function, vascular coverage, blood-brain barrier permeability and immune cell migration may be related to amyloid toxicity, oxidative stress and apolipoprotein E (APOE) genotype. These vascular deficits may in turn contribute to parenchymal amyloid deposition, neurotoxicity, glial activation and metabolic dysfunction in multiple cell types. A vicious feedback cycle ensues, with progressively worsening neuronal and vascular pathology through the course of the disease. Thus, a better appreciation for the importance of vascular dysfunction in AD may open new avenues for research and therapy.

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“…At the level of IF, both osmotic and hydrostatic pressures contribute to a bulk convection flow, which allows waste compounds to be removed from IF to venular PS, and from there to the cerebral venous lymphatic system (Plog & Nedergaard, 2018). GlyS plays a critical role in Aβ clearance from the IF (Iliff et al., 2012) together with other clearance pathways, involving the BBB (Cockerill, Oliver, Xu, Fu, & Zhu, 2018). Furthermore, recently it has been shown that GlyS function is strictly regulated by Sleep/wake (S/W) cycle (Iliff et al., 2012; Xie et al., 2013), and Aβ clearance fluctuates in parallel with GlyS along the cycle, being higher during sleep and lower in wakefulness (Xie et al., 2013).…”

Section: Evidence and Mechanisms Of Nvu Alteration In Admentioning

confidence: 99%

Locus Coeruleus and neurovascular unit: From its role in physiology to its potential role in Alzheimer’s disease pathogenesis

Giorgi

Galgani²,

Puglisi-Allegra

et al. 2020

J of Neuroscience Research

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Locus coeruleus (LC) is the main noradrenergic (NA) nucleus of the central nervous system. LC degenerates early during Alzheimer's disease (AD) and NA loss might concur to AD pathogenesis. Aside from neurons, LC terminals provide dense innervation of brain intraparenchymal arterioles/capillaries, and NA modulates astrocyte functions. The term neurovascular unit (NVU) defines the strict anatomical/functional interaction occurring between neurons, glial cells, and brain vessels. NVU plays a fundamental role in coupling the energy demand of activated brain regions with regional cerebral blood flow, it includes the blood-brain barrier (BBB), plays an active role in neuroinflammation, and participates also to the glymphatic system. NVU alteration is involved in AD pathophysiology through several mechanisms, mainly related to a relative oligoemia in activated brain regions and impairment of structural and functional BBB integrity, which contributes also to the intracerebral accumulation of insoluble amyloid. We review the existing data on the morphological features of LC-NA innervation of the NVU, as well as its contribution to neurovascular coupling and BBB proper functioning. After introducing the main experimental data linking LC with AD, which have repeatedly shown a key role of neuroinflammation and increased amyloid plaque formation, we discuss the potential mechanisms by which the loss of NVU modulation by LC might contribute to AD pathogenesis. Surprisingly, thus far not so many studies have tested directly these mechanisms in models of AD in which LC has been lesioned experimentally. Clarifying the interaction of LC with NVU in AD pathogenesis may disclose potential therapeutic targets for AD.

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Blood-Brain Barrier Integrity and Clearance of Amyloid-β from the BBB

Cited by 48 publications

References 23 publications

Lipopolysaccharide-Induced Neuroinflammation as a Bridge to Understand Neurodegeneration

Lipopolysaccharide-Induced Neuroinflammation as a Bridge to Understand Neurodegeneration

Vascular Dysfunction in Alzheimer’s Disease: A Prelude to the Pathological Process or a Consequence of It?

Locus Coeruleus and neurovascular unit: From its role in physiology to its potential role in Alzheimer’s disease pathogenesis

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