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Amyloid Fibrils

Abeta(1-40) fibril

Amyloid fibrils are peptide or protein aggregates that form under certain conditions in vitro or in vivo. For example, the amyloid fibril plaques found in brain tissue of Alzheimer patients are formed from the peptide Aβ and are associated with neurodegeneration. Amyloid formation is also observed with other diseases, such as type II diabetes and Creutzfeldt-Jakob disease.

Amyloid structures represent an alternative to the native folding pattern of many peptides and proteins. A characteristic motif of this folding pattern is the cross-β structure in which the peptides or proteins associate by β-sheet formation within protofilaments making up a fibril.

In collaboration with Marcus Fändrich (Ulm University, Germany), we study the molecular architecture of amyloid fibrils associated with human disease. Our goal is to identify fundamental principles of amyloid formation, and potential targets for disease treatment. The Figure shows an 8 Å structure of an Aβ(1-40) fibril [1]. At this resolution, the path of the peptide can be identified.

Other publications on the topic: [2][3][1][4][5][6][7][8][9][10][11][12]


  1. Sachse, C, Fändrich M, Grigorieff N.  2008.  Paired beta-sheet structure of an Aβ(1-40) amyloid fibril revealed by electron microscopy. Proc Natl Acad Sci U S A. 105:7462-6.
  2. Sachse, C, Xu C, Wieligmann K, Diekmann S, Grigorieff N, Fändrich M.  2006.  Quaternary structure of a mature amyloid fibril from Alzheimer's Aβ(1-40) peptide. J Mol Biol. 362:347-54.
  3. Sachse, C, Chen JZ, Coureux PD, Stroupe ME, Fändrich M, Grigorieff N.  2007.  High-resolution electron microscopy of helical specimens: a fresh look at tobacco mosaic virus. J Mol Biol. 371:812-35.
  4. Sachse, C, Grigorieff N, Fändrich M.  2009.  Elektronenmikroskopie an Alzheimer-Fibrillen. Bioforum. 32:26-28.
  5. Meinhardt, J, Sachse C, Hortschansky P, Grigorieff N, Fändrich M.  2009.  Aβ(1-40) fibril polymorphism implies diverse interaction patterns in amyloid fibrils. J Mol Biol. 386:869-77.
  6. Fändrich, M, Meinhardt J, Grigorieff N.  2009.  Structural polymorphism of Alzheimer Aβ and other amyloid fibrils. Prion. 3:89-93.
  7. Schmidt, M, Sachse C, Richter W, Xu C, Fändrich M, Grigorieff N.  2009.  Comparison of Alzheimer Aβ(1-40) and Aβ(1-42) amyloid fibrils reveals similar protofilament structures. Proc Natl Acad Sci U S A. 106(47):19813-8.
  8. Sachse, C, Grigorieff N, Fändrich M.  2010.  Nanoscale flexibility parameters of Alzheimer amyloid fibrils determined by electron cryo-microscopy. Angew Chem Int Ed Engl. 49:1321–1323.
  9. Fändrich, M, Schmidt M, Grigorieff N.  2011.  Recent progress in understanding Alzheimer's β-amyloid structures. Trends Biochem. Sci. 36:338-45.
  10. Schmidt, M, Rohou A, Lasker K, Yadav JK, Schiene-Fischer C, Fändrich M, Grigorieff N.  2015.  Peptide Dimer Structure in an Aβ(1-42) Fibril Visualized with Cryo-EM. Proc Natl Acad Sci U S A. 112:11858-11863.
  11. Schmidt, A, Annamalai K, Schmidt M, Grigorieff N, Marcus Fändrich M.  2016.  Cryo-EM reveals the steric zipper structure of a light chain-derived amyloid fibril. Proc Natl Acad Sci U S A. 113:6200–6205.
  12. Close, W, Neumann M, Schmidt A, Hora M, Annamalai K, Schmidt M, Reif B, Schmidt V, Grigorieff N, Fändrich M.  2018.  Physical basis of amyloid fibril polymorphism. Nature Communications. 9:1-7.