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Cessation of Neoangiogenesis in Alzheimer's Disease Follows Amyloid-beta Immunization
Pathogenic neoangiogenesis in Alzheimer's disease (AD) is due to amyloid-beta (Aβ) and results in blood-brain barrier (BBB) leakiness in AD. It likely occurs as a compensatory response to impaired cerebral blood flow and provides a strong link between brain vascularity and AD. Aβ immunotherapy...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3584312/ https://www.ncbi.nlm.nih.gov/pubmed/23446889 http://dx.doi.org/10.1038/srep01354 |
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author | Biron, Kaan E. Dickstein, Dara L. Gopaul, Rayshad Fenninger, Franz Jefferies, Wilfred A. |
author_facet | Biron, Kaan E. Dickstein, Dara L. Gopaul, Rayshad Fenninger, Franz Jefferies, Wilfred A. |
author_sort | Biron, Kaan E. |
collection | PubMed |
description | Pathogenic neoangiogenesis in Alzheimer's disease (AD) is due to amyloid-beta (Aβ) and results in blood-brain barrier (BBB) leakiness in AD. It likely occurs as a compensatory response to impaired cerebral blood flow and provides a strong link between brain vascularity and AD. Aβ immunotherapy is an experimental treatment for AD; however, unexpected negative vascular side effects seen in early human clinical trials demonstrate that our knowledge of Aβ and AD pathogenesis is incomplete. We demonstrate that immunization with Aβ peptides neutralizes the amyloid trigger leading to neoangiogenesis and reverses hypervascularity in Tg2576 AD mice. This process resolves plaque burden suggesting that neoangiogenesis is a key mechanism underlying plaque formation. A meta-analysis demonstrated that hypervascular reversion in vaccinated Alzheimer's patients. This appears to be the first example of vascular reversion following any therapeutic intervention and supports the conclusion that modulation of neoangiogenesis may repair damage in the AD brain. |
format | Online Article Text |
id | pubmed-3584312 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-35843122013-02-28 Cessation of Neoangiogenesis in Alzheimer's Disease Follows Amyloid-beta Immunization Biron, Kaan E. Dickstein, Dara L. Gopaul, Rayshad Fenninger, Franz Jefferies, Wilfred A. Sci Rep Article Pathogenic neoangiogenesis in Alzheimer's disease (AD) is due to amyloid-beta (Aβ) and results in blood-brain barrier (BBB) leakiness in AD. It likely occurs as a compensatory response to impaired cerebral blood flow and provides a strong link between brain vascularity and AD. Aβ immunotherapy is an experimental treatment for AD; however, unexpected negative vascular side effects seen in early human clinical trials demonstrate that our knowledge of Aβ and AD pathogenesis is incomplete. We demonstrate that immunization with Aβ peptides neutralizes the amyloid trigger leading to neoangiogenesis and reverses hypervascularity in Tg2576 AD mice. This process resolves plaque burden suggesting that neoangiogenesis is a key mechanism underlying plaque formation. A meta-analysis demonstrated that hypervascular reversion in vaccinated Alzheimer's patients. This appears to be the first example of vascular reversion following any therapeutic intervention and supports the conclusion that modulation of neoangiogenesis may repair damage in the AD brain. Nature Publishing Group 2013-02-28 /pmc/articles/PMC3584312/ /pubmed/23446889 http://dx.doi.org/10.1038/srep01354 Text en Copyright © 2013, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/ |
spellingShingle | Article Biron, Kaan E. Dickstein, Dara L. Gopaul, Rayshad Fenninger, Franz Jefferies, Wilfred A. Cessation of Neoangiogenesis in Alzheimer's Disease Follows Amyloid-beta Immunization |
title | Cessation of Neoangiogenesis in Alzheimer's Disease Follows Amyloid-beta Immunization |
title_full | Cessation of Neoangiogenesis in Alzheimer's Disease Follows Amyloid-beta Immunization |
title_fullStr | Cessation of Neoangiogenesis in Alzheimer's Disease Follows Amyloid-beta Immunization |
title_full_unstemmed | Cessation of Neoangiogenesis in Alzheimer's Disease Follows Amyloid-beta Immunization |
title_short | Cessation of Neoangiogenesis in Alzheimer's Disease Follows Amyloid-beta Immunization |
title_sort | cessation of neoangiogenesis in alzheimer's disease follows amyloid-beta immunization |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3584312/ https://www.ncbi.nlm.nih.gov/pubmed/23446889 http://dx.doi.org/10.1038/srep01354 |
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