Format

Send to

Choose Destination
Langmuir. 2012 Sep 4;28(35):12711-21. doi: 10.1021/la3021436. Epub 2012 Aug 22.

Aggregation pathways of the amyloid β(1-42) peptide depend on its colloidal stability and ordered β-sheet stacking.

Author information

1
Department of Chemistry and Biochemistry, California State University, Los Angeles, Los Angeles, California 90032, United States.

Abstract

Amyloid β (Aβ) fibrils are present as a major component in senile plaques, the hallmark of Alzheimer's disease (AD). Diffuse plaques (nonfibrous, loosely packed Aβ aggregates) containing amorphous Aβ aggregates are also formed in brain. This work examines the influence of Cu(2+) complexation by Aβ on the aggregation process in the context of charge and structural variations. Changes in the surface charges of Aβ molecules due to Cu(2+) binding, measured with a ζ-potential measurement device, were correlated with the aggregate morphologies examined by atomic force microscopy. As a result of the charge variation, the "colloid-like" stability of the aggregation intermediates, which is essential to the fibrillation process, is affected. Consequently, Cu(2+) enhances the amorphous aggregate formation. By monitoring variations in the secondary structures with circular dichroism spectroscopy, a direct transformation from the unstructured conformation to the β-sheet structure was observed for all types of aggregates observed (oligomers, fibrils, and/or amorphous aggregates). Compared to the Aβ aggregation pathway in the absence of Cu(2+) and taking other factors affecting Aβ aggregation (i.e., pH and temperature) into account, our investigation indicates that formations of amorphous and fibrous aggregates diverge from the same β-sheet-containing partially folded intermediate. This study suggests that the hydrophilic domain of Aβ also plays a role in the Aβ aggregation process. A kinetic model was proposed to account for the effects of the Cu(2+) binding on these two aggregation pathways in terms of charge and structural variations.

PMID:
22870885
PMCID:
PMC3464049
DOI:
10.1021/la3021436
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for American Chemical Society Icon for PubMed Central
Loading ...
Support Center