Following spatial Aβ aggregation dynamics in evolving Alzheimer’s disease pathology by imaging stable isotope labeling kinetics
Wojciech Michno, Katie Stringer, Thomas Enzlein, Melissa K. Passarelli, Stéphane Escrig, Karina S. Vitanova, Jack Wood, Kaj Blennow, Henrik Zetterberg, Anders Meibom, Carsten Hopf, Frances A. Edwards, Jörg Hanrieder
Abstract
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.