title: Molecular structure of β-amyloid fibrils in Alzheimer's disease brain tissue.
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.
authors.affiliation: Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0520, USA.
authors.forename: Jun-Xia
authors.initials: JX
authors.lastname: Lu
authors.forename: Wei
authors.initials: W
authors.lastname: Qiang
authors.forename: Wai-Ming
authors.initials: WM
authors.lastname: Yau
authors.forename: Charles D
authors.initials: CD
authors.lastname: Schwieters
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Meredith
authors.forename: Robert
authors.initials: R
authors.lastname: Tycko
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000473:pathology*; D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D008954:Models, Biological
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides
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