Zinc ion rapidly induces toxic, off-pathway amyloid-β oligomers distinct from amyloid-β derived diffusible ligands in Alzheimer's disease.

ABSTRACT: Alzheimer's disease (AD) is the most prevalent neurodegenerative disease in the elderly. Zinc (Zn) ion interacts with the pathogenic hallmark, amyloid-β (Aβ), and is enriched in senile plaques in brain of AD patients. To understand Zn-chelated Aβ (ZnAβ) species, here we systematically characterized ZnAβ aggregates by incubating equimolar Aβ with Zn. We found ZnAβ40 and ZnAβ42 both form spherical oligomers with a diameter of ~12-14 nm composed of reduced β-sheet content. Oligomer assembly examined by analytical ultracentrifugation, hydrophobic exposure by BisANS spectra, and immunoreactivity of ZnAβ and Aβ derived diffusible ligands (ADDLs) are distinct. The site-specific ¹³C labeled solid-state NMR spectra showed that ZnAβ40 adopts β-sheet structure as in Aβ40 fibrils. Interesti

SUBMITTER: Lee MC 

PROVIDER: S-EPMC5859292 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature