1 Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
2 Department of Neuroscience, Physiology, and Pharmacology, University College London, London, UK.
3 Center for Mass Spectrometry and Optical Spectroscopy, Mannheim University of Applied Sciences, Mannheim, Germany.
4 Laboratory of Biological Geochemistry, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
5 Department of Chemistry and Biochemistry, Concordia University, Montréal, Québec, Canada.
6 Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
7 Department of Neurodegenerative Disease, Queen Square Institute of Neurology, University College London, London, UK.
8 UK Dementia Research Institute, University College London, London, UK.
9 Center for Advanced Surface Analysis, Institute of Earth Sciences, University of Lausanne, Lausanne, Switzerland.
10 Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden. jh@gu.se.

ß-Amyloid (Aß) 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 Aß pathology is initiated and where and when distinct Aß 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 Aß deposition through ongoing plaque development. This allowed visualizing Aß aggregation dynamics within single plaques across different brain regions. We show that formation of structurally distinct plaques is associated with differential Aß peptide deposition. Specifically, Aß1-42 is forming an initial core structure followed by radial outgrowth and late secretion and deposition of Aß1-38. These data describe a detailed picture of the earliest events of precipitating amyloid pathology at scales not previously possible.