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Seeded strain‐like transmission of β‐amyloid morphotypes in APP transgenic mice

Götz Heilbronner, Yvonne S Eisele, Franziska Langer, Stephan A Kaeser, Renata Novotny, Amudha Nagarathinam, Andreas Åslund, Per Hammarström, K Peter R Nilsson, Mathias Jucker

Author Affiliations

  1. Götz Heilbronner1,2,
  2. Yvonne S Eisele1,2,
  3. Franziska Langer1,2,
  4. Stephan A Kaeser1,2,
  5. Renata Novotny1,2,3,
  6. Amudha Nagarathinam1,2,
  7. Andreas Åslund4,
  8. Per Hammarström4,
  9. K Peter R Nilsson4 and
  10. Mathias Jucker*,1,2
  1. 1 Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, D‐72076, Tübingen, Germany
  2. 2 DZNE, German Center for Neurodegenerative Diseases, D‐72076, Tübingen, Germany
  3. 3 Graduate School of Cellular and Molecular Neuroscience, University of Tübingen, D‐72074, Tübingen, Germany
  4. 4 Department of Chemistry, IFM, Linköping University, SE‐581 83, Linköping, Sweden
  1. *Corresponding author. Tel:+49 7071 29 86863: Fax:+49 7071 29 4521; E-mail: mathias.jucker{at}uni-tuebingen.de
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Abstract

The polymorphic β‐amyloid lesions present in individuals with Alzheimer's disease are collectively known as cerebral β‐amyloidosis. Amyloid precursor protein (APP) transgenic mouse models similarly develop β‐amyloid depositions that differ in morphology, binding of amyloid conformation‐sensitive dyes, and Aβ40/Aβ42 peptide ratio. To determine the nature of such β‐amyloid morphotypes, β‐amyloid‐containing brain extracts from either aged APP23 brains or aged APPPS1 brains were intracerebrally injected into the hippocampus of young APP23 or APPPS1 transgenic mice. APPPS1 brain extract injected into young APP23 mice induced β‐amyloid deposition with the morphological, conformational, and Aβ40/Aβ42 ratio characteristics of β‐amyloid deposits in aged APPPS1 mice, whereas APP23 brain extract injected into young APP23 mice induced β‐amyloid deposits with the characteristics of β‐amyloid deposits in aged APP23 mice. Injecting the two extracts into the APPPS1 host revealed a similar difference between the induced β‐amyloid deposits, although less prominent, and the induced deposits were similar to the β‐amyloid deposits found in aged APPPS1 hosts. These results indicate that the molecular composition and conformation of aggregated Aβ in APP transgenic mice can be maintained by seeded conversion.

  • Received March 26, 2013.
  • Revision received August 12, 2013.
  • Accepted August 12, 2013.
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