Blood-Brain Barrier Leakage in Patients with Early Alzheimer Disease

Haar, Harm J. van de; Burgmans, Saartje; Jansen, Jacobus F.A.; Osch, Matthias J.P. van; Buchem, Mark A. van; Muller, Majon; Hofman, Paul; Verhey, Frans R.J.; Backes, Walter H.

doi:10.1148/radiol.2017164043

Cited by 102 publications

(121 citation statements)

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“…Considerable evidence suggests that the BBB integrity is compromised in AD patients (Glenner, , ; Powers et al , ; Zipser et al , ; Zlokovic, ). In patients with mild cognitive impairment, or early stages of AD, the age‐dependent changes of the BBB permeability are accelerated compared to neurological normal individuals (Montagne et al , ; van de Haar et al , ). This suggests that neurovascular dysfunction may be an early occurrence in the pathogenesis of AD.…”

Section: Altered Metabolism In Neurodegenerative Disordersmentioning

confidence: 99%

Brain metabolism in health, aging, and neurodegeneration

2017

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Brain cells normally respond adaptively to bioenergetic challenges resulting from ongoing activity in neuronal circuits, and from environmental energetic stressors such as food deprivation and physical exertion. At the cellular level, such adaptive responses include the "strengthening" of existing synapses, the formation of new synapses, and the production of new neurons from stem cells. At the molecular level, bioenergetic challenges result in the activation of transcription factors that induce the expression of proteins that bolster the resistance of neurons to the kinds of metabolic, oxidative, excitotoxic, and proteotoxic stresses involved in the pathogenesis of brain disorders including stroke, and Alzheimer's and Parkinson's diseases. Emerging findings suggest that lifestyles that include intermittent bioenergetic challenges, most notably exercise and dietary energy restriction, can increase the likelihood that the brain will function optimally and in the absence of disease throughout life. Here, we provide an overview of cellular and molecular mechanisms that regulate brain energy metabolism, how such mechanisms are altered during aging and in neurodegenerative disorders, and the potential applications to brain health and disease of interventions that engage pathways involved in neuronal adaptations to metabolic stress.

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Section: Altered Metabolism In Neurodegenerative Disordersmentioning

confidence: 99%

Brain metabolism in health, aging, and neurodegeneration

2017

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“…It should be noted that increased BBB permeability through gadolinium leakage was observed in the hippocampus of patients with mild cognitive impairment (MCI) and several grey and white matter regions in early Alzheimer's disease (AD) patients. However, the degree of disruption may vary from patient to patient, since only 25% of patients with MCI and 45-78% of early AD patients were found to have brain microbleeds [52][53][54]. In this respect, AD animal models have also had limited success in predicting clinical outcomes.…”

Section: Contradictory Findings Across Animal Models Of Neurological mentioning

confidence: 99%

In vitro modeling of the neurovascular unit: advances in the field

Bhalerao

Sivandzade

Archie

et al. 2020

Fluids Barriers CNS

118

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The blood-brain barrier (BBB) is a fundamental component of the central nervous system. Its functional and structural integrity is vital in maintaining the homeostasis of the brain microenvironment. On the other hand, the BBB is also a major hindering obstacle for the delivery of effective therapies to treat disorders of the Central Nervous System (CNS). Over time, various model systems have been established to simulate the complexities of the BBB. The development of realistic in vitro BBB models that accurately mimic the physiological characteristics of the brain microcapillaries in situ is of fundamental importance not only in CNS drug discovery but also in translational research. Successful modeling of the Neurovascular Unit (NVU) would provide an invaluable tool that would aid in dissecting out the pathological factors, mechanisms of action, and corresponding targets prodromal to the onset of CNS disorders. The field of BBB in vitro modeling has seen many fundamental changes in the last few years with the introduction of novel tools and methods to improve existing models and enable new ones. The development of CNS organoids, organ-on-chip, spheroids, 3D printed microfluidics, and other innovative technologies have the potential to advance the field of BBB and NVU modeling. Therefore, in this review, summarize the advances and progress in the design and application of functional in vitro BBB platforms with a focus on rapidly advancing technologies.The BBB consists of highly specialized vascular endothelial cells (EC) lining the brain microvessels in juxtaposition with closely associated pericytes [1], extracellular matrix components, and astrocytic end-feet processes [2]. Along with other cells such as neurons and microglia, this cellular milieu modulates the BBB properties, supports its viability and functions [3]. At the brain microvascular level, the BBB functions as a highly dynamic and active interface between the systemic circulation and the CNS. The BBB maintains a stable brain environment to protect the CNS from unsolicited cells, bacteria, viruses, and potentially harmful substances (either endogenous or exogenous) apart from protecting against systemic fluctuations. The BBB also regulates the transport of essential molecules and nutrients necessary to maintain the optimal CNS environment and support neuronal activities [4]. The BBB responds to many physiological and pathological cues, including rheological changes [5], inflammatory stimuli, oxidative stress [6], diabetes, and hypercholesterolemia [7-10], acute brain injury [3], etc. The intrinsically unique and utmost complex functional interaction between the BBB endothelium and the surrounding cellular milieu (including astrocytes, pericytes, neurons, microglia, myocytes as well as specialized cellular compartments such as endothelial glycocalyx [11,12] has been termed "neurovascular unit (NVU)" [2,13]. In addition, the basement membrane, which exerts essential functions in cellular support and signal transduction,

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“…Thus, the unique properties of the BBB help to maintain brain homeostasis and protect the brain from exposure to different toxins and pathogens, as well as injuries . Recent studies have identified BBB leakage in early stage AD patients, manifested by increased permeability of the BBB, decreased levels of tight junction proteins and reduced Aβ clearance . The exact cause of BBB dysfunction in AD has not yet been identified.…”

Section: Brain‐on‐a‐chipmentioning

confidence: 99%

“…[103,104] Recent studies have identified BBB leakage in early stage AD patients, manifested by increased permeability of the BBB, decreased levels of tight junction proteins and reduced Ab clearance. [105] The exact cause of BBB dysfunction in AD hasn ot yet been identified.…”

Section: The Role Of Neuroinflammation and Blood Brain Barrier In Admentioning

confidence: 99%

Go with the Flow—Microfluidics Approaches for Amyloid Research

Zilberzwige‐Tal

Gazit

2018

Chemistry An Asian Journal

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The rapid development of cost-efficient microfluidic devices has received tremendous attention from scientists of diverse fields. The growing potential of utilizing microfluidic platforms has further advanced the ability to integrate existing technology into microfluidic devices. Thus, allowing scientists to approach questions in fundamental fields, such as amyloid research, using new and otherwise unachievable conditions. Amyloids are associated with neurodegeneration and are in the forefront of many research efforts worldwide. The newly emerged microfluidic technology can serve as a novel research tool providing a platform for developing new methods in this field. In this review, we summarize the recent progress in amyloid research using microfluidic approaches. These approaches are driven from various fields, including physical chemistry, electrochemistry, biochemistry, and cell biology. Moreover, the new insights into novel microfluidic approaches for amyloid research reviewed here can be easily modified for other research interests.

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Blood-Brain Barrier Leakage in Patients with Early Alzheimer Disease

Cited by 102 publications

References 0 publications

Brain metabolism in health, aging, and neurodegeneration

Brain metabolism in health, aging, and neurodegeneration

In vitro modeling of the neurovascular unit: advances in the field

Go with the Flow—Microfluidics Approaches for Amyloid Research

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