Unknown

Dataset Information

0

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

altmetric image

Publications

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]

Similar Datasets

| S-EPMC7848700 | biostudies-literature
| S-EPMC6820800 | biostudies-other
| S-EPMC2678625 | biostudies-literature
| S-EPMC1297669 | biostudies-literature
| S-EPMC2587602 | biostudies-literature
| S-EPMC5953852 | biostudies-literature
| S-EPMC5233555 | biostudies-literature
| S-EPMC9481533 | biostudies-literature
| S-EPMC3074258 | biostudies-literature
| S-EPMC4679000 | biostudies-literature