Molecular structure of ß-amyloid fibrils in Alzheimer's disease brain tissue.
Cell
; 154(6): 1257-68, 2013 Sep 12.
Article
em En
| MEDLINE
| ID: mdl-24034249
ABSTRACT
In vitro, ß-amyloid (Aß) 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 Aß 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 Aß (Aß40) fibril structure in each patient; however, the structures were different from one another. A molecular structural model developed for Aß40 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Encéfalo
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Doença de Alzheimer
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Amiloide
Tipo de estudo:
Prognostic_studies
Limite:
Aged
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Female
/
Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article