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

Molecular structure of β-amyloid fibrils in Alzheimer's disease brain tissue.

Author information

1
Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0520, USA.

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.

PMID:
24034249
PMCID:
PMC3814033
DOI:
10.1016/j.cell.2013.08.035
[Indexed for MEDLINE]
Free PMC Article

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