Molecular structure of ß-amyloid fibrils in Alzheimer's disease brain tissue.
Cell
; 154(6): 1257-68, 2013 Sep 12.
Article
en 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
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Encéfalo
/
Enfermedad de Alzheimer
/
Amiloide
Tipo de estudio:
Prognostic_studies
Límite:
Aged
/
Female
/
Humans
Idioma:
En
Revista:
Cell
Año:
2013
Tipo del documento:
Article
País de afiliación:
Estados Unidos