Atomic-resolution structure of a disease-relevant Aβ(1–42) amyloid fibril

Amyloid-β (Aβ) is present in humans as a 39- to 42-amino acid residue metabolic product of the amyloid precursor protein. Although the two predominant forms, Aβ(1-40) and Aβ(1-42), differ in only two residues, they display different biophysical, biological, and clinical behavior. Aβ(1-42) is the more neurotoxic species, aggregates much faster, and dominates in senile plaque of Alzheimer's disease (AD) patients. Although small Aβ oligomers are believed to be the neurotoxic species, Aβ amyloid fibrils are, because of their presence in plaques, a pathological hallmark of AD and appear to play an important role in disease progression through cell-to-cell transmissibility. Here, we solved the 3D structure of a…

• NS
  National Science Foundation

  Award: DE-SC0012704
• UD
  U.S. Department of Energy

  Award: SC0012704
• AN
  Agence Nationale de la Recherche

  Awards: ANR-14-CE09-0024B, ANR-11-BSV8-021-01
• SN
  Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung

  Awards: 200020_146757, 200020_159707
• OO
  Office of Science

  Awards: SC0012704, DE-SC0012704
• BA
  Biological and Environmental Research

  Award: DE-SC0012704
• BN
  Brookhaven National Laboratory

  Award: SC0012704