Molecular Structure of β-amyloid Fibrils in Alzheimer's Disease Brain Tissue

Cell. 2013 Sep 12;154(6):1257-68. doi: 10.1016/j.cell.2013.08.035.

Abstract

In vitro, β-amyloid (Aβ) peptides form polymorphic fibrils, with molecular structures that depend on growth conditions, plus various oligomeric and protofibrillar aggregates. Here, we investigate structures of human brain-derived Aβ fibrils, using seeded fibril growth from brain extract and data from solid-state nuclear magnetic resonance and electron microscopy. Experiments on tissue from two Alzheimer's disease (AD) patients with distinct clinical histories showed a single predominant 40 residue Aβ (Aβ40) fibril structure in each patient; however, the structures were different from one another. A molecular structural model developed for Aβ40 fibrils from one patient reveals features that distinguish in-vivo- from in-vitro-produced fibrils. The data suggest that fibrils in the brain may spread from a single nucleation site, that structural variations may correlate with variations in AD, and that structure-specific amyloid imaging agents may be an important future goal.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Aged
  • Alzheimer Disease / pathology*
  • Amyloid / chemistry*
  • Amyloid / metabolism
  • Amyloid / ultrastructure
  • Amyloid beta-Peptides / chemistry
  • Amyloid beta-Peptides / metabolism
  • Brain / metabolism
  • Brain / pathology*
  • Female
  • Humans
  • Models, Biological

Substances

  • Amyloid
  • Amyloid beta-Peptides

Associated data

  • PDB/2M4J