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Anti-Aβ Antibodies and Cerebral Amyloid Angiopathy Complications

Cerebral amyloid angiopathy (CAA) corresponds to the deposition of amyloid material in the cerebral vasculature, leading to structural modifications of blood vessel walls. The most frequent form of sporadic CAA involves fibrillar β-amyloid peptide (Aβ) deposits, mainly the 40 amino acid form (Aβ(1−4...

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Autores principales: Chantran, Yannick, Capron, Jean, Alamowitch, Sonia, Aucouturier, Pierre
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6620823/
https://www.ncbi.nlm.nih.gov/pubmed/31333665
http://dx.doi.org/10.3389/fimmu.2019.01534
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author Chantran, Yannick
Capron, Jean
Alamowitch, Sonia
Aucouturier, Pierre
author_facet Chantran, Yannick
Capron, Jean
Alamowitch, Sonia
Aucouturier, Pierre
author_sort Chantran, Yannick
collection PubMed
description Cerebral amyloid angiopathy (CAA) corresponds to the deposition of amyloid material in the cerebral vasculature, leading to structural modifications of blood vessel walls. The most frequent form of sporadic CAA involves fibrillar β-amyloid peptide (Aβ) deposits, mainly the 40 amino acid form (Aβ(1−40)), which are commonly found in the elderly with or without Alzheimer's disease. Sporadic CAA usually remains clinically silent. However, in some cases, acute complications either hemorrhagic or inflammatory can occur. Similar complications occurred after active or passive immunization against Aβ in experimental animal models exhibiting CAA, and in subjects with Alzheimer's disease during clinical trials. The triggering of these adverse events by active immunization and monoclonal antibody administration in CAA-bearing individuals suggests that analogous mechanisms could be involved during spontaneous CAA complications, drawing particular attention to the role of anti-Aβ antibodies. However, antibodies that react with several monomeric and aggregated forms of Aβ spontaneously occur in virtually all human individuals, hence being part of the “natural antibody” repertoire. Natural antibodies are usually described as having low-affinity and high cross-reactivity toward microbial components and autoantigens. Although frequently of the IgM class, they also belong to IgG and IgA isotypes. They likely display homeostatic functions and protective roles in aging. Until recently, the peculiar properties of these natural antibodies have hindered proper analysis of the Aβ-reactive antibody repertoire and the study of their implication in CAA complications. Herein, we review and comment the evidences of an auto-immune nature of spontaneous CAA complications, and discuss implications for forthcoming research and clinical practice.
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spelling pubmed-66208232019-07-22 Anti-Aβ Antibodies and Cerebral Amyloid Angiopathy Complications Chantran, Yannick Capron, Jean Alamowitch, Sonia Aucouturier, Pierre Front Immunol Immunology Cerebral amyloid angiopathy (CAA) corresponds to the deposition of amyloid material in the cerebral vasculature, leading to structural modifications of blood vessel walls. The most frequent form of sporadic CAA involves fibrillar β-amyloid peptide (Aβ) deposits, mainly the 40 amino acid form (Aβ(1−40)), which are commonly found in the elderly with or without Alzheimer's disease. Sporadic CAA usually remains clinically silent. However, in some cases, acute complications either hemorrhagic or inflammatory can occur. Similar complications occurred after active or passive immunization against Aβ in experimental animal models exhibiting CAA, and in subjects with Alzheimer's disease during clinical trials. The triggering of these adverse events by active immunization and monoclonal antibody administration in CAA-bearing individuals suggests that analogous mechanisms could be involved during spontaneous CAA complications, drawing particular attention to the role of anti-Aβ antibodies. However, antibodies that react with several monomeric and aggregated forms of Aβ spontaneously occur in virtually all human individuals, hence being part of the “natural antibody” repertoire. Natural antibodies are usually described as having low-affinity and high cross-reactivity toward microbial components and autoantigens. Although frequently of the IgM class, they also belong to IgG and IgA isotypes. They likely display homeostatic functions and protective roles in aging. Until recently, the peculiar properties of these natural antibodies have hindered proper analysis of the Aβ-reactive antibody repertoire and the study of their implication in CAA complications. Herein, we review and comment the evidences of an auto-immune nature of spontaneous CAA complications, and discuss implications for forthcoming research and clinical practice. Frontiers Media S.A. 2019-07-04 /pmc/articles/PMC6620823/ /pubmed/31333665 http://dx.doi.org/10.3389/fimmu.2019.01534 Text en Copyright © 2019 Chantran, Capron, Alamowitch and Aucouturier. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Chantran, Yannick
Capron, Jean
Alamowitch, Sonia
Aucouturier, Pierre
Anti-Aβ Antibodies and Cerebral Amyloid Angiopathy Complications
title Anti-Aβ Antibodies and Cerebral Amyloid Angiopathy Complications
title_full Anti-Aβ Antibodies and Cerebral Amyloid Angiopathy Complications
title_fullStr Anti-Aβ Antibodies and Cerebral Amyloid Angiopathy Complications
title_full_unstemmed Anti-Aβ Antibodies and Cerebral Amyloid Angiopathy Complications
title_short Anti-Aβ Antibodies and Cerebral Amyloid Angiopathy Complications
title_sort anti-aβ antibodies and cerebral amyloid angiopathy complications
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6620823/
https://www.ncbi.nlm.nih.gov/pubmed/31333665
http://dx.doi.org/10.3389/fimmu.2019.01534
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