Abstract
We have investigated physical properties of microvasculature and vessel association with microglial clusters in cortical tissue from Alzheimer disease individuals, classified as severe (ADsev) or mild (ADmild), and nondemented controls (ND). Immunostaining with laminin or von Willebrand factor demonstrated numbers of microvessels and microvascular density were significantly higher in ADsev cases compared with levels in ADmild or ND cases suggesting proangiogenic activity in ADsev brain. Evidence for extravascular laminin immunoreactivity was found in ADsev tissue and was largely absent in ADmild and ND cases suggesting vascular remodeling in ADsev brain included abnormalities in blood vessels. Microgliosis was progressively increased from ND to ADmild to ADsev with the latter demonstrating areas of clustered microglia (groupings of three or more cells) rarely observed in ADmild or ND cases. Microglial clusters in ADsev brain were in close proximity with extravascular laminin and also plasma protein, fibrinogen, implicating vascular perturbation as a component of inflammatory reactivity. ADsev brain also exhibited elevated levels of the proinflammatory/ angiogenic factors tumor necrosis factor-α (TNF-α) and vascular endothelial growth factor (VEGF) in association, relative to non-association, with microglial clusters. The presence of extravascular laminin and fibrinogen and the vascular modifying factors, TNF-α and VEGF in localization with clusters of activated microglia, is consistent with microglial- induced vascular remodeling in ADsev brain. Microglial-vascular reciprocal interactions could serve a critical role in the amplification and perpetuation of inflammatory reactivity in AD brain.
Keywords: Alzheimer disease, microglial clusters, perturbed angiogenesis, extravascular laminin and fibrinogen, TNF-α, VEGF, leaky blood brain barrier.
Current Alzheimer Research
Title: Converging Perturbed Microvasculature and Microglial Clusters Characterize Alzheimer Disease Brain
Volume: 7 Issue: 7
Author(s): N. Jantaratnotai, C. Schwab, J. K. Ryu, P. L. McGeer and J. G. McLarnon
Affiliation:
Keywords: Alzheimer disease, microglial clusters, perturbed angiogenesis, extravascular laminin and fibrinogen, TNF-α, VEGF, leaky blood brain barrier.
Abstract: We have investigated physical properties of microvasculature and vessel association with microglial clusters in cortical tissue from Alzheimer disease individuals, classified as severe (ADsev) or mild (ADmild), and nondemented controls (ND). Immunostaining with laminin or von Willebrand factor demonstrated numbers of microvessels and microvascular density were significantly higher in ADsev cases compared with levels in ADmild or ND cases suggesting proangiogenic activity in ADsev brain. Evidence for extravascular laminin immunoreactivity was found in ADsev tissue and was largely absent in ADmild and ND cases suggesting vascular remodeling in ADsev brain included abnormalities in blood vessels. Microgliosis was progressively increased from ND to ADmild to ADsev with the latter demonstrating areas of clustered microglia (groupings of three or more cells) rarely observed in ADmild or ND cases. Microglial clusters in ADsev brain were in close proximity with extravascular laminin and also plasma protein, fibrinogen, implicating vascular perturbation as a component of inflammatory reactivity. ADsev brain also exhibited elevated levels of the proinflammatory/ angiogenic factors tumor necrosis factor-α (TNF-α) and vascular endothelial growth factor (VEGF) in association, relative to non-association, with microglial clusters. The presence of extravascular laminin and fibrinogen and the vascular modifying factors, TNF-α and VEGF in localization with clusters of activated microglia, is consistent with microglial- induced vascular remodeling in ADsev brain. Microglial-vascular reciprocal interactions could serve a critical role in the amplification and perpetuation of inflammatory reactivity in AD brain.
Export Options
About this article
Cite this article as:
Jantaratnotai N., Schwab C., K. Ryu J., L. McGeer P. and G. McLarnon J., Converging Perturbed Microvasculature and Microglial Clusters Characterize Alzheimer Disease Brain, Current Alzheimer Research 2010; 7 (7) . https://dx.doi.org/10.2174/156720510793499039
DOI https://dx.doi.org/10.2174/156720510793499039 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
Call for Papers in Thematic Issues
New Advances in the Prevention, Diagnosis, Treatment, and Rehabilitation of Alzheimer's Disease
Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...read more
Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
Deep Learning for Advancing Alzheimer's Disease Research
Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
Diagnostic and therapeutic biomarkers of dementia
Dementia affects 18 million people worldwide. Dementia is a syndrome of symptoms caused by brain disease, usually chronic or progressive, clinically characterized by multiple impairments of higher cortical functions such as memory, thinking, orientation, and learning. In addition, in the course of dementia, cognitive deficits are observed, which often hinder ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
The Antioxidant Activities of Natural Polysaccharides
Current Drug Targets Is Brain-Derived Neurotrophic Factor: A Common Link Between Neurodegenerative Disorders and Cancer?
Current Alzheimer Research Meet Our Editorial Board Member
Current Neuropharmacology Reserve Mechanisms in Neurodegenerative Diseases: From Bench to Bedside and Back Again
Current Medicinal Chemistry Advances in Characterization of Neuroprotective Peptide, Humanin
Current Medicinal Chemistry Natural Animal Models of Neurodegenerative Protein Misfolding Diseases
Current Pharmaceutical Design Common Cellular and Molecular Mechanisms Underlying Alzheimer’s Disease and Type 2 Diabetes: A Knowledge-Driven Approach
CNS & Neurological Disorders - Drug Targets The NGF Metabolic Pathway in the CNS and its Dysregulation in Down Syndrome and Alzheimer’s Disease
Current Alzheimer Research A Comparison Between Quetiapine and Aripiprazole for Treatment of Schizophrenia: A Double Blind Contrast
Current Psychopharmacology Editorial (Thematic Issue: “Pregnancy in Women with Metabolic Syndrome”)
Current Pharmaceutical Biotechnology Hydroxypyridinone Derivatives: A Fascinating Class of Chelators with Therapeutic Applications - An Update
Current Medicinal Chemistry Anti-Amyloid Effects of Small Molecule Aβ-Binding Agents in PS1/APP Mice
Letters in Drug Design & Discovery New Developments in Anti-Platelet Therapies Potential Use of CD39/Vascular ATP Diphosphohydrolase in Thrombotic Disorders
Current Drug Targets Cardiovascular Adverse Effects of Anti-Inflammatory Drugs
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Role of Glycosphingolipids and Therapeutic Perspectives on Alzheimers Disease
CNS & Neurological Disorders - Drug Targets Metabolic Syndrome: Clinical Features Leading to Therapeutic Strategies
Vascular Disease Prevention (Discontinued) Altered Glutamate Neurotransmission and Behaviour in Dementia: Evidence from Studies of Memantine
Current Molecular Pharmacology Fused 1,4-Dihydropyridines as Potential Calcium Modulatory Compounds
Mini-Reviews in Medicinal Chemistry Rheumatoid Arthritis and Cardiovascular Risk: Between Lights and Shadows
Current Rheumatology Reviews Impact of Drug Metabolism/Pharmacokinetics and their Relevance Upon Traditional Medicine-based Cardiovascular Drug Research
Current Drug Metabolism