Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2021
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
_version_ 1783708979281526784
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
work_keys_str_mv AT michnowojciech followingspatialabaggregationdynamicsinevolvingalzheimersdiseasepathologybyimagingstableisotopelabelingkinetics
AT stringerkatiem followingspatialabaggregationdynamicsinevolvingalzheimersdiseasepathologybyimagingstableisotopelabelingkinetics
AT enzleinthomas followingspatialabaggregationdynamicsinevolvingalzheimersdiseasepathologybyimagingstableisotopelabelingkinetics
AT passarellimelissak followingspatialabaggregationdynamicsinevolvingalzheimersdiseasepathologybyimagingstableisotopelabelingkinetics
AT escrigstephane followingspatialabaggregationdynamicsinevolvingalzheimersdiseasepathologybyimagingstableisotopelabelingkinetics
AT vitanovakarina followingspatialabaggregationdynamicsinevolvingalzheimersdiseasepathologybyimagingstableisotopelabelingkinetics
AT woodjack followingspatialabaggregationdynamicsinevolvingalzheimersdiseasepathologybyimagingstableisotopelabelingkinetics
AT blennowkaj followingspatialabaggregationdynamicsinevolvingalzheimersdiseasepathologybyimagingstableisotopelabelingkinetics
AT zetterberghenrik followingspatialabaggregationdynamicsinevolvingalzheimersdiseasepathologybyimagingstableisotopelabelingkinetics
AT meibomanders followingspatialabaggregationdynamicsinevolvingalzheimersdiseasepathologybyimagingstableisotopelabelingkinetics
AT hopfcarsten followingspatialabaggregationdynamicsinevolvingalzheimersdiseasepathologybyimagingstableisotopelabelingkinetics
AT edwardsfrancesa followingspatialabaggregationdynamicsinevolvingalzheimersdiseasepathologybyimagingstableisotopelabelingkinetics
AT hanriederjorg followingspatialabaggregationdynamicsinevolvingalzheimersdiseasepathologybyimagingstableisotopelabelingkinetics