β-Carotene, a Potent Amyloid Aggregation Inhibitor, Promotes Disordered Aβ Fibrillar Structure

Abstract

The aggregation of amyloid beta (Aβ) into fibrillar aggregates is a key feature of Alzheimer’s disease (AD) pathology. β-carotene and related compounds have been shown to associate with amyloid aggregates and have direct impact on the formation of amyloid fibrils. However, the precise effect of β-carotene on the structure of amyloid aggregates is not known, which poses a limitation towards developing it as a potential AD therapeutic. In this report, we use nanoscale AFM-IR spectroscopy to probe the structure of Aβ oligomers and fibrils at the single aggregate level and demonstrate that the main effect of β-carotene towards modulating Aβ aggregation is not to inhibit fibril formation but to alter the secondary structure of the fibrils and promote fibrils that lack the characteristic ordered beta structure.

Keywords

• β-carotene
• amyloid aggregation
• AFM-IR
• fibril structure
• beta-sheet