Molecular basis for amyloid-β polymorphism

Jacques Philippe Colletier, Arthur Laganowsky, Meytal Landau, Minglei Zhao, Angela B. Soriaga, Lukasz Goldschmidt, David Flot, Duilio Cascio, Michael R. Sawaya, David Eisenberg

Research output: Contribution to journalArticlepeer-review


Amyloid-beta (Aβ) aggregates are the main constituent of senile plaques, the histological hallmark of Alzheimer's disease. Aβ molecules form β-sheet containing structures that assemble into a variety of polymorphic oligomers, protofibers, and fibers that exhibit a range of lifetimes and cellular toxicities. This polymorphic nature of Aβ has frustrated its biophysical characterization, its structural determination, and our understanding of its pathological mechanism. To elucidate Aβ polymorphism in atomic detail, we determined eight new microcrystal structures of fiber-forming segments of Aβ. These structures, all of short, self-complementing pairs of β-sheets termed steric zippers, reveal a variety of modes of self-association of Aβ. Combining these atomic structures with previous NMR studies allows us to propose several fiber models, offering molecular models for some of the repertoire of polydisperse structures accessible to Aβ. These structures and molecular models contribute fundamental information for understanding Aβpolymorphic nature and pathogenesis.

Original languageEnglish
Pages (from-to)16938-16943
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number41
StatePublished - 11 Oct 2011
Externally publishedYes


  • 3D profile
  • Amyloid aggregation
  • Heterotypic zipper
  • Protofilaments

All Science Journal Classification (ASJC) codes

  • General


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