Following spatial Aβ aggregation dynamics in evolving Alzheimer's disease pathology by imaging stable isotope labeling kinetics

Michno, Wojciech, 1992 (author): Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry

Stringer, K. M. (author)

Enzlein, T. (author)

Passarelli, M. K. (author)

Escrig, S. (author)

Vitanova, K. (author)

Wood, J. (author)

Blennow, Kaj, 1958 (author): Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry

Zetterberg, Henrik, 1973 (author): Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry

Meibom, A. (author)

Hopf, C. (author)

Edwards, F. A. (author)

Hanrieder, Jörg, 1980 (author): Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry

(creator_code:org_t)

American Association for the Advancement of Science (AAAS), 2021
2021
English.
In: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 7:25

Related links:: https://www.science....; show more...; https://gup.ub.gu.se...; https://doi.org/10.1...; show less...

Abstract Subject headings

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 APPNL-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. Copyright © 2021 The Authors, some rights reserved.

MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)

By the author/editor: Michno, Wojciech ...; Stringer, K. M.; Enzlein, T.; Passarelli, M. K ...; Escrig, S.; Vitanova, K.; show more...; Wood, J.; Blennow, Kaj, 19 ...; Zetterberg, Henr ...; Meibom, A.; Hopf, C.; Edwards, F. A.; Hanrieder, Jörg, ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Neurosciences

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