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Following spatial Aβ aggregation dynamics in evolving Alzheimer’s disease pathology by imaging stable isotope labeling kinetics
β-Amyloid (Aβ) plaque formation is the major pathological hallmark of Alzheimer’s disease (AD) and constitutes a potentially critical, early inducer driving AD pathogenesis as it precedes other pathological events and cognitive symptoms by decades. It is therefore critical to understand how Aβ patho...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208724/ https://www.ncbi.nlm.nih.gov/pubmed/34134980 http://dx.doi.org/10.1126/sciadv.abg4855 |
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author | Michno, Wojciech Stringer, Katie M. Enzlein, Thomas Passarelli, Melissa K. Escrig, Stephane Vitanova, Karina Wood, Jack Blennow, Kaj Zetterberg, Henrik Meibom, Anders Hopf, Carsten Edwards, Frances A. Hanrieder, Jörg |
author_facet | Michno, Wojciech Stringer, Katie M. Enzlein, Thomas Passarelli, Melissa K. Escrig, Stephane Vitanova, Karina Wood, Jack Blennow, Kaj Zetterberg, Henrik Meibom, Anders Hopf, Carsten Edwards, Frances A. Hanrieder, Jörg |
author_sort | Michno, Wojciech |
collection | PubMed |
description | β-Amyloid (Aβ) plaque formation is the major pathological hallmark of Alzheimer’s disease (AD) and constitutes a potentially critical, early inducer driving AD pathogenesis as it precedes other pathological events and cognitive symptoms by decades. It is therefore critical to understand how Aβ pathology is initiated and where and when distinct Aβ species aggregate. Here, we used metabolic isotope labeling in APP(NL-G-F) knock-in mice together with mass spectrometry imaging to monitor the earliest seeds of Aβ deposition through ongoing plaque development. This allowed visualizing Aβ aggregation dynamics within single plaques across different brain regions. We show that formation of structurally distinct plaques is associated with differential Aβ peptide deposition. Specifically, Aβ1-42 is forming an initial core structure followed by radial outgrowth and late secretion and deposition of Aβ1-38. These data describe a detailed picture of the earliest events of precipitating amyloid pathology at scales not previously possible. |
format | Online Article Text |
id | pubmed-8208724 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-82087242021-06-28 Following spatial Aβ aggregation dynamics in evolving Alzheimer’s disease pathology by imaging stable isotope labeling kinetics Michno, Wojciech Stringer, Katie M. Enzlein, Thomas Passarelli, Melissa K. Escrig, Stephane Vitanova, Karina Wood, Jack Blennow, Kaj Zetterberg, Henrik Meibom, Anders Hopf, Carsten Edwards, Frances A. Hanrieder, Jörg Sci Adv Research Articles β-Amyloid (Aβ) plaque formation is the major pathological hallmark of Alzheimer’s disease (AD) and constitutes a potentially critical, early inducer driving AD pathogenesis as it precedes other pathological events and cognitive symptoms by decades. It is therefore critical to understand how Aβ pathology is initiated and where and when distinct Aβ species aggregate. Here, we used metabolic isotope labeling in APP(NL-G-F) knock-in mice together with mass spectrometry imaging to monitor the earliest seeds of Aβ deposition through ongoing plaque development. This allowed visualizing Aβ aggregation dynamics within single plaques across different brain regions. We show that formation of structurally distinct plaques is associated with differential Aβ peptide deposition. Specifically, Aβ1-42 is forming an initial core structure followed by radial outgrowth and late secretion and deposition of Aβ1-38. These data describe a detailed picture of the earliest events of precipitating amyloid pathology at scales not previously possible. American Association for the Advancement of Science 2021-06-16 /pmc/articles/PMC8208724/ /pubmed/34134980 http://dx.doi.org/10.1126/sciadv.abg4855 Text en Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Research Articles Michno, Wojciech Stringer, Katie M. Enzlein, Thomas Passarelli, Melissa K. Escrig, Stephane Vitanova, Karina Wood, Jack Blennow, Kaj Zetterberg, Henrik Meibom, Anders Hopf, Carsten Edwards, Frances A. Hanrieder, Jörg Following spatial Aβ aggregation dynamics in evolving Alzheimer’s disease pathology by imaging stable isotope labeling kinetics |
title | Following spatial Aβ aggregation dynamics in evolving Alzheimer’s disease pathology by imaging stable isotope labeling kinetics |
title_full | Following spatial Aβ aggregation dynamics in evolving Alzheimer’s disease pathology by imaging stable isotope labeling kinetics |
title_fullStr | Following spatial Aβ aggregation dynamics in evolving Alzheimer’s disease pathology by imaging stable isotope labeling kinetics |
title_full_unstemmed | Following spatial Aβ aggregation dynamics in evolving Alzheimer’s disease pathology by imaging stable isotope labeling kinetics |
title_short | Following spatial Aβ aggregation dynamics in evolving Alzheimer’s disease pathology by imaging stable isotope labeling kinetics |
title_sort | following spatial aβ aggregation dynamics in evolving alzheimer’s disease pathology by imaging stable isotope labeling kinetics |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208724/ https://www.ncbi.nlm.nih.gov/pubmed/34134980 http://dx.doi.org/10.1126/sciadv.abg4855 |
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