Acta Neuropathologica

, Volume 128, Issue 4, pp 477–484 | Cite as

Aβ seeds resist inactivation by formaldehyde

  • Sarah K. Fritschi
  • Amarallys Cintron
  • Lan Ye
  • Jasmin Mahler
  • Anika Bühler
  • Frank Baumann
  • Manuela Neumann
  • K. Peter R. Nilsson
  • Per Hammarström
  • Lary C. Walker
  • Mathias Jucker
Original Paper

Abstract

Cerebral β-amyloidosis can be exogenously induced by the intracerebral injection of brain extracts containing aggregated β-amyloid (Aβ) into young, pre-depositing Aβ precursor protein- (APP) transgenic mice. Previous work has shown that the induction involves a prion-like seeding mechanism in which the seeding agent is aggregated Aβ itself. Here we report that the β-amyloid-inducing activity of Alzheimer’s disease (AD) brain tissue or aged APP-transgenic mouse brain tissue is preserved, albeit with reduced efficacy, after formaldehyde fixation. Moreover, spectral analysis with amyloid conformation-sensitive luminescent conjugated oligothiophene dyes reveals that the strain-like properties of aggregated Aβ are maintained in fixed tissues. The resistance of Aβ seeds to inactivation and structural modification by formaldehyde underscores their remarkable durability, which in turn may contribute to their persistence and spread within the body. The present findings can be exploited to establish the relationship between the molecular structure of Aβ aggregates and the variable clinical features and disease progression of AD even in archived, formalin-fixed autopsy material.

Keywords

Amyloid Alzheimer Prion Fixation Strain 

Notes

Acknowledgments

We would like to thank Matthias Staufenbiel for the APP23 tg mice and comments on the manuscript; Markus Fändrich (Ulm, Germany) for the recombinant Aβ; Yvonne Eisele, Jan Winchenbach, Maria Mina, Christian Krüger, Ulrike Obermüller, Jörg Odenthal, Jeromy Dooyema, Sofie Nyström and many other members of our departments for experimental help and discussions. The assistance of Jay Rasmussen (Lethbridge, Canada) and Rodrigo Morales (Houston, USA) is greatly appreciated. This work was supported by grants from the Competence Network on Degenerative Dementias (BMBF-01GI0705), the National Institutes of Health (R21AG040589, P51RR165, P51OD11132 and R36AG043646), the MetLife Foundation, and by the Swedish Research Council.

Supplementary material

401_2014_1339_MOESM1_ESM.pdf (3.3 mb)
Supplementary material 1 (PDF 3376 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Sarah K. Fritschi
    • 1
    • 2
    • 3
  • Amarallys Cintron
    • 4
  • Lan Ye
    • 1
    • 2
    • 3
  • Jasmin Mahler
    • 1
    • 2
    • 3
  • Anika Bühler
    • 1
    • 2
  • Frank Baumann
    • 1
    • 2
  • Manuela Neumann
    • 1
    • 6
  • K. Peter R. Nilsson
    • 7
  • Per Hammarström
    • 7
  • Lary C. Walker
    • 4
    • 5
  • Mathias Jucker
    • 1
    • 2
  1. 1.German Center for Neurodegenerative Diseases (DZNE)TübingenGermany
  2. 2.Department of Cellular Neurology, Hertie Institute for Clinical Brain ResearchUniversity of TübingenTübingenGermany
  3. 3.Graduate School of Cellular and Molecular NeuroscienceUniversity of TübingenTübingenGermany
  4. 4.Yerkes National Primate Research CenterEmory UniversityAtlantaUSA
  5. 5.Department of NeurologyEmory UniversityAtlantaUSA
  6. 6.Department of NeuropathologyUniversity of TübingenTübingenGermany
  7. 7.Department of Chemistry, IFMLinköping UniversityLinköpingSweden

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