Thrombin and inflammatory proteins are elevated in Alzheimer's disease microvessels: Implications for disease pathogenesis

Grammas, Paula; Samany, Pezhman Ghatreh; Thirumangalakudi, Lakshmi

doi:10.3233/jad-2006-9105

Cited by 143 publications

(130 citation statements)

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“…In addition, HIF-1 expression was observed in the control groups, apart from case 3. The HIF-1 increases in Alzheimer's patients may be explained as a response to exposed hypoxia; such observations have already been described in similar studies (6,7,19). Increasing HIF-1 expression was shown to be dependent on the age in the control groups.…”

Section: Discussionsupporting

confidence: 58%

“…HIF-1 activation promotes a cellular response to hypoxia for cell survival (17,18), and HIF-1 activity can prevent neuron death and ameliorate these symptoms of neurodegenerative disorders such as AD (18). Grammas et al (19) reported that HIF-1α is elevated in brain blood vessels in Alzheimer's patients compared to in control groups. Grammas et al (6) reported in another study that brain sections from AD and control mice demonstrated that HIF-1α, angiopoietin-2, matrix metalloproteinase 2, and caspase 3 are elevated and Bcl-xL decreased in the microvasculature of AD mice.…”

Section: Discussionmentioning

confidence: 99%

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Immunohistochemical Determination of HIF, TSP-1, ADAMTS1, and ADAMTS8 Expressions in the Brains of Alzheimer’s Disease Patients: A Preliminary Autopsy Study

İnanır¹,

Eren²,

Fedakar³

et al. 2016

Erciyes Med J

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Objective: Alzheimer's disease (AD) is a progressive neurodegenerative disease that mostly affects the elderly population. Recent studies performed in AD highlight the pathophysiological relevance of disintegrin and metalloproteinase with thrombospondin type 1-like motifs (ADAMTS) genes and their products, namely hypoxia inducible factor-1 (HIF-1) and thrombospondin-1 (TSP-1). Thus, the aim of this study was to describe and identify the distribution, characteristics, and any changes in the expression and immunoreactivity for HIF-1, TSP-1, and ADAMTS1 and 8 in AD brains. Materials and Methods:Nine patients who were autopsied in the Council of Forensic Medicine, Bursa Morgue Department in 2013, were selected. All patients were sent for autopsy to the Morgue Department within 8 h after death. At the autopsy, tissue samples of the organs were obtained for histopathological examination for determining the cause of death. Among these, two patients were clinically diagnosed with AD.Results: Immunohistochemical staining was performed, and the staining intensity/extensity was evaluated using a semiquantitative scoring system. Median distribution (extensity) scores of the immunohistochemical staining were estimated as 2 for HIF-1, 0.67 for TSP-1, 3.11 for ADAMTS1, and 2.78 for ADAMTS8. Intensity scores were estimated as 1.22 for HIF-1, 0.56 for TSP-1, 3 for ADAMTS1, and 2.11 for ADAMTS8. Conclusion:Our study suggests that ADAMTS1 and ADAMTS8 expressions are not specific for AD. To understand and provide definitive data on all aspects of metalloproteinases, extracellular matrix proteins, and transcriptional factor effects to AD, further studies are needed, where other metalloproteinases and related molecules/enzymes should be studied.

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Section: Discussionsupporting

confidence: 58%

Section: Discussionmentioning

confidence: 99%

Immunohistochemical Determination of HIF, TSP-1, ADAMTS1, and ADAMTS8 Expressions in the Brains of Alzheimer’s Disease Patients: A Preliminary Autopsy Study

İnanır¹,

Eren²,

Fedakar³

et al. 2016

Erciyes Med J

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“…Furthermore, thrombin and its propeptide, prothrombin, are produced by neurons and glia in the CNS (6,7). Clinical studies have postulated that thrombin regulation may play an important role in the neurodegeneration associated with Alzheimer's Disease (8) and Multiple Sclerosis (9).…”

Section: Introductionmentioning

confidence: 99%

Concentration-Dependent Dual Role of Thrombin in Protection of Cultured Rat Cortical Neurons

et al. 2015

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“…BBB dysfunction mediates the indirect neurotoxic effects of chronic hypoperfusion by promoting oxidative stress [6,15,16], inflammation [17][18][19][20], impaired glucose transport across the BBB [21][22][23], BBB permeability [21,24,25], and dysregulation of nitric oxide (NO) [26][27][28], a key mediator of vascular tone and regional blood flow regulation [29,30]. As such, BBB dysfunction could mediate a vicious circle in which cerebral perfusion is reduced further and the neurodegenerative process is ac- [47,48], and by post mortem studies showing coexisting cerebrovascular disease in most AD patients [6,[49][50][51].…”

Section: Introductionmentioning

confidence: 99%

Vascular dysfunction in the pathogenesis of Alzheimer's disease — A review of endothelium-mediated mechanisms and ensuing vicious circles

Marco

Venneri

Farkas

et al. 2015

Neurobiology of Disease

223

179

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Article available under the terms of the CC-BY-NC-ND licence (https://creativecommons.org/licenses/by-nc-nd/4.0/) eprints@whiterose.ac.uk https://eprints.whiterose.ac.uk/ Reuse Unless indicated otherwise, fulltext items are protected by copyright with all rights reserved. The copyright exception in section 29 of the Copyright, Designs and Patents Act 1988 allows the making of a single copy solely for the purpose of non-commercial research or private study within the limits of fair dealing. The publisher or other rights-holder may allow further reproduction and re-use of this version -refer to the White Rose Research Online record for this item. Where records identify the publisher as the copyright holder, users can verify any specific terms of use on the publisher's website. TakedownIf you consider content in White Rose Research Online to be in breach of UK law, please notify us by emailing eprints@whiterose.ac.uk including the URL of the record and the reason for the withdrawal request.

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Thrombin and inflammatory proteins are elevated in Alzheimer's disease microvessels: Implications for disease pathogenesis

Cited by 143 publications

References 0 publications

Immunohistochemical Determination of HIF, TSP-1, ADAMTS1, and ADAMTS8 Expressions in the Brains of Alzheimer’s Disease Patients: A Preliminary Autopsy Study

Immunohistochemical Determination of HIF, TSP-1, ADAMTS1, and ADAMTS8 Expressions in the Brains of Alzheimer’s Disease Patients: A Preliminary Autopsy Study

Concentration-Dependent Dual Role of Thrombin in Protection of Cultured Rat Cortical Neurons

Vascular dysfunction in the pathogenesis of Alzheimer's disease — A review of endothelium-mediated mechanisms and ensuing vicious circles

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