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Epitope Mapping Immunoassay Analysis of the Interaction between β-Amyloid and Fibrinogen

The vast majority of patients with Alzheimer’s disease (AD) suffer from impaired cerebral circulation. Substantial evidence indicates that fibrinogen (Fbg) and fibrin clot formation play an important role in this circulatory dysfunction in AD. Fbg interacts with β-amyloid (1-42) (Aβ), forming plasmi...

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Autores principales: Van Giau, Vo, An, Seong Soo A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6387197/
https://www.ncbi.nlm.nih.gov/pubmed/30678343
http://dx.doi.org/10.3390/ijms20030496
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author Van Giau, Vo
An, Seong Soo A.
author_facet Van Giau, Vo
An, Seong Soo A.
author_sort Van Giau, Vo
collection PubMed
description The vast majority of patients with Alzheimer’s disease (AD) suffer from impaired cerebral circulation. Substantial evidence indicates that fibrinogen (Fbg) and fibrin clot formation play an important role in this circulatory dysfunction in AD. Fbg interacts with β-amyloid (1-42) (Aβ), forming plasmin-resistant abnormal blood clots, and increased fibrin deposition has been discovered in the brains of AD patients and mouse models. In this study, biochemical approaches and the epitope mapping immunoassay were employed to characterize binding epitopes within the Fbg and complementary epitopes in Aβ. We discovered the Aβ5–25 peptide as the most critical region for the interaction, which can be inhibited by specific monoclonal and polyclonal antibodies against the central region of Aβ. Aβ binding to Fbg may block plasmin-mediated fibrin cleavage at this site, resulting in the generation of increased levels of plasmin-resistant fibrin degradation fragments. Our study elucidates the Aβ–Fbg interaction that may involve the mechanism by which Aβ–Fbg binding delays fibrinolysis by plasmin, providing valuable information in the development of therapeutic approaches for AD.
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spelling pubmed-63871972019-02-27 Epitope Mapping Immunoassay Analysis of the Interaction between β-Amyloid and Fibrinogen Van Giau, Vo An, Seong Soo A. Int J Mol Sci Article The vast majority of patients with Alzheimer’s disease (AD) suffer from impaired cerebral circulation. Substantial evidence indicates that fibrinogen (Fbg) and fibrin clot formation play an important role in this circulatory dysfunction in AD. Fbg interacts with β-amyloid (1-42) (Aβ), forming plasmin-resistant abnormal blood clots, and increased fibrin deposition has been discovered in the brains of AD patients and mouse models. In this study, biochemical approaches and the epitope mapping immunoassay were employed to characterize binding epitopes within the Fbg and complementary epitopes in Aβ. We discovered the Aβ5–25 peptide as the most critical region for the interaction, which can be inhibited by specific monoclonal and polyclonal antibodies against the central region of Aβ. Aβ binding to Fbg may block plasmin-mediated fibrin cleavage at this site, resulting in the generation of increased levels of plasmin-resistant fibrin degradation fragments. Our study elucidates the Aβ–Fbg interaction that may involve the mechanism by which Aβ–Fbg binding delays fibrinolysis by plasmin, providing valuable information in the development of therapeutic approaches for AD. MDPI 2019-01-24 /pmc/articles/PMC6387197/ /pubmed/30678343 http://dx.doi.org/10.3390/ijms20030496 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Van Giau, Vo
An, Seong Soo A.
Epitope Mapping Immunoassay Analysis of the Interaction between β-Amyloid and Fibrinogen
title Epitope Mapping Immunoassay Analysis of the Interaction between β-Amyloid and Fibrinogen
title_full Epitope Mapping Immunoassay Analysis of the Interaction between β-Amyloid and Fibrinogen
title_fullStr Epitope Mapping Immunoassay Analysis of the Interaction between β-Amyloid and Fibrinogen
title_full_unstemmed Epitope Mapping Immunoassay Analysis of the Interaction between β-Amyloid and Fibrinogen
title_short Epitope Mapping Immunoassay Analysis of the Interaction between β-Amyloid and Fibrinogen
title_sort epitope mapping immunoassay analysis of the interaction between β-amyloid and fibrinogen
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6387197/
https://www.ncbi.nlm.nih.gov/pubmed/30678343
http://dx.doi.org/10.3390/ijms20030496
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