Molecular mechanisms of globular–shaped Aβ oligomer promoting amyloid aggregation in low–molecular–weight Aβ42

Abstract

We focused on globular–shaped amyloid β–protein (Aβ) oligomer (gAβO), a part of high–molecular–weight Aβ oligomers among the various fractions in amyloid aggregation, and examined the molecular interactions of gAβO extracted from size exclusion chromatography. Thioflavin T analysis and high–speed atomic force microscopy revealed that gAβO did not show fibril formation, but had a facilitating effect for Aβ aggregation, especially primary nucleation and fibril elongation in low–molecular–weight Aβ42. Furthermore, the promoting effect of gAβO was influenced by the coexistence of mature Aβ42 fibril seeds. Our results indicate that gAβO is a highly toxic fraction of Aβ aggregates that is deeply involved in the pathogenesis of Alzheimer disease, especially in the early stages of the disease.