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Amyloid β and free heme: bloody new insights into the pathogenesis of Alzheimer’s disease

The cerebral formation of Amyloid β (Aβ) is a critical pathological feature of Alzheimer’s disease (AD). An accumulation of this peptide as senile plaques (SP) was already reported by Alois Alzheimer, the discoverer of the disease. Yet the exact contribution of Aβ to AD development remains elusive....

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Autores principales: Flemmig, Jörg, Zámocký, Marcel, Alia, A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Medknow Publications & Media Pvt Ltd 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6065240/
https://www.ncbi.nlm.nih.gov/pubmed/30028317
http://dx.doi.org/10.4103/1673-5374.235021
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author Flemmig, Jörg
Zámocký, Marcel
Alia, A
author_facet Flemmig, Jörg
Zámocký, Marcel
Alia, A
author_sort Flemmig, Jörg
collection PubMed
description The cerebral formation of Amyloid β (Aβ) is a critical pathological feature of Alzheimer’s disease (AD). An accumulation of this peptide as senile plaques (SP) was already reported by Alois Alzheimer, the discoverer of the disease. Yet the exact contribution of Aβ to AD development remains elusive. Moreover, while extensive cerebral Aβ formation leads to fibril formation in many species, AD-like symptoms apparently depend on the highly conserved N-terminal residues R5, Y10 and H13. The amino acids were also shown to lead to the formation of Aβ-heme complexes, which exhibit peroxidase activity in the presence of H(2)O(2). Taking together these observations we propose that the formation and enzymatic activity of the named complexes may represent an essential aspect of AD pathology. Furthermore, Aβ is also known to lead to cerebral micro-vessel destruction (CAA) as well as to hemolytic events. Thus we suggest that the Aβ-derived cerebral accumulation of blood-derived free heme represents a likely precondition for the subsequent formation of Aβ-heme complexes.
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spelling pubmed-60652402018-08-09 Amyloid β and free heme: bloody new insights into the pathogenesis of Alzheimer’s disease Flemmig, Jörg Zámocký, Marcel Alia, A Neural Regen Res Review The cerebral formation of Amyloid β (Aβ) is a critical pathological feature of Alzheimer’s disease (AD). An accumulation of this peptide as senile plaques (SP) was already reported by Alois Alzheimer, the discoverer of the disease. Yet the exact contribution of Aβ to AD development remains elusive. Moreover, while extensive cerebral Aβ formation leads to fibril formation in many species, AD-like symptoms apparently depend on the highly conserved N-terminal residues R5, Y10 and H13. The amino acids were also shown to lead to the formation of Aβ-heme complexes, which exhibit peroxidase activity in the presence of H(2)O(2). Taking together these observations we propose that the formation and enzymatic activity of the named complexes may represent an essential aspect of AD pathology. Furthermore, Aβ is also known to lead to cerebral micro-vessel destruction (CAA) as well as to hemolytic events. Thus we suggest that the Aβ-derived cerebral accumulation of blood-derived free heme represents a likely precondition for the subsequent formation of Aβ-heme complexes. Medknow Publications & Media Pvt Ltd 2018-07 /pmc/articles/PMC6065240/ /pubmed/30028317 http://dx.doi.org/10.4103/1673-5374.235021 Text en Copyright: © Neural Regeneration Research http://creativecommons.org/licenses/by-nc-sa/4.0 This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.
spellingShingle Review
Flemmig, Jörg
Zámocký, Marcel
Alia, A
Amyloid β and free heme: bloody new insights into the pathogenesis of Alzheimer’s disease
title Amyloid β and free heme: bloody new insights into the pathogenesis of Alzheimer’s disease
title_full Amyloid β and free heme: bloody new insights into the pathogenesis of Alzheimer’s disease
title_fullStr Amyloid β and free heme: bloody new insights into the pathogenesis of Alzheimer’s disease
title_full_unstemmed Amyloid β and free heme: bloody new insights into the pathogenesis of Alzheimer’s disease
title_short Amyloid β and free heme: bloody new insights into the pathogenesis of Alzheimer’s disease
title_sort amyloid β and free heme: bloody new insights into the pathogenesis of alzheimer’s disease
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6065240/
https://www.ncbi.nlm.nih.gov/pubmed/30028317
http://dx.doi.org/10.4103/1673-5374.235021
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