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

ABSTRACT: In vitro, ?-amyloid (A?) 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 A? 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 A? (A?40) fibril structure in each patient; however, the structures were different from one another. A molecular structural model developed for A?40 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.

SUBMITTER: Lu JX

PROVIDER: S-EPMC3814033 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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

Lu Jun-Xia JX Qiang Wei W Yau Wai-Ming WM Schwieters Charles D CD Meredith Stephen C SC Tycko Robert R

Cell 20130901 6

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 resid ...[more]

PMID: 24034249

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