The DOI matches its Crossref record; 16 of the 16 references it cites were found in a registry or an index.
Neuroinflammation and Blood-Brain Barrier Changes in Capillary Amyloid Angiopathy
Abstract
INTRODUCTION: β-Amyloid (Aβ) accumulation in cortical capillaries is a variant of cerebral amyloid angiopathy (CAA) referred to as capillary CAA (capCAA). capCAA is associated with a neuroinflammatory response. In vitro studies indicate that Aβ induces reactive oxygen species (ROS) production, mainly generated through NADPH oxidase (NOX), by activated microglia. ROS in turn can induce altered expression of tight junctions (TJ), which are essential for blood-brain barrier (BBB) function. Whether the function of the BBB is affected in the brains of Alzheimer's disease (AD) patients with comorbid capCAA remains elusive. Cases with capCAA and no other AD-related changes allow studying capCAA-associated BBB alterations independent of AD pathology. AIM: In this study, we have investigated BBB alterations in capCAA and addressed the role of the neuroinflammatory response. METHODS: Human postmortem brain tissue with capCAA was analyzed by immunohistochemical staining. RESULTS: In this study, we show for the first time a dramatic loss of TJ proteins claudin-5, occludin and ZO-1 in Aβ-laden capillaries. In addition, affected capillaries are associated with clusters of NOX-2-positive activated microglia. Disrupted BBB function was observed by increased presence of fibrinogen around the affected capillaries. CONCLUSIONS: Our data provide support for the early observation that neuroinflammatory response is involved in the altered expression of TJs in endothelial cells and loss of BBB integrity in capCAA.
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“Accumulation of the β-amyloid, a key characteristic of AD, was demonstrated to compromise BBB permeability by decreasing expression of TJ proteins, including claudin-5, occluding and ZO-1 [123].”
From Designing and optimizing AAV-mediated gene therapy for neurodegenerative diseases: from bench to bedside (2024) · cites this paper as [123]
In the citing paper
“These alterations in cytokine expression can increase the permeability of the BBB and play a crucial role in activating several signaling pathways located in different brain cells (Carrano et al., 2012).”
From Arbovirus infection increases the risk for the development of neurodegenerative disease pathology in the murine model (2024) · cites this paper as Carrano et al., 2012
In the citing paper
“Additionally, human CAA post-mortem capillaries with amyloid-β load are surrounded by NOX2-positive microglia [122,123].”
From ROS Generation in Microglia: Understanding Oxidative Stress and Inflammation in Neurodegenerative Disease (2020) · cites this paper as [123]
Citations
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Simpson, D. S. A., & Oliver, P. L. (2020) · Antioxidants · doi:10.3390/antiox9080743 · Cited by 1,044
Functional morphology of the blood–brain barrier in health and disease
Liebner, S., Dijkhuizen, R. M., Reiss, Y., Plate, K. H., Agalliu, D., & Constantin, G. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1815-1 · Cited by 872
The blood-brain barrier in Alzheimer’s disease
Zenaro, E., Piacentino, G., & Constantin, G. (2017) · Neurobiology of Disease · doi:10.1016/j.nbd.2016.07.007 · Cited by 767
Interaction between Aβ and Tau in the Pathogenesis of Alzheimer’s Disease
Zhang, H., Wei, W., Zhao, M., Ma, L., Jiang, X., Pei, H., Cao, Y., & Li, H. (2021) · International Journal of Biological Sciences · doi:10.7150/ijbs.57078 · Cited by 689
Blood-Brain Barrier Dysfunction and the Pathogenesis of Alzheimer’s Disease
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Metadata
- Authors
- Carrano, A., Hoozemans, J. J. M., van der Vies, S. M., van Horssen, J., de Vries, H. E., & Rozemuller, A. J. M.
- Affiliations
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- Venue
- Neurodegenerative Diseases
- Publisher
- S. Karger AG
- Published
- 2012
- Volume
- 10
- Issue
- 1-4
- Pages
- 329-331
- ISSN
- 1660-2854 (ISSN-L)
- 1660-2862
- OpenAlex
- W1974295585
- Cited by
- 186
- References
- 16
- Citations by year
- 2026: 12 · 2025: 15 · 2024: 19 · 2023: 22 · 2022: 17 · 2021: 29 · 2020: 18 · 2019: 8 · 2018: 11 · 2017: 5 · 2016: 9 · 2015: 2 · 2014: 7 · 2013: 9 · 2012: 1
- FWCI
- 3.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurodegenerative Diseases (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Pure Amsterdam UMC (submittedVersion)
- VU Research Portal (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Clinical Neurology › Intracerebral and Subarachnoid Hemorrhage Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Keywords
- amyloid-beta, blood-brain barrier, neuroinflammation, tight junctions, claudin-5, occludin, ZO-1, NADPH oxidase, NOX2, microglial activation, reactive oxygen species, fibrinogen, Alzheimer's disease, postmortem brain
- MeSH terms
- Blood Proteins, Blood-Brain Barrier, Brain, Capillaries, Encephalitis, Fibrinogen, Humans, Membrane Proteins, Phosphoproteins, Cohort Studies, Amyloid beta-Peptides, Cerebral Amyloid Angiopathy, Tight Junctions, NADPH Oxidases, Claudins, Claudin-5, Occludin, Zonula Occludens-1 Protein
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