Exogenous amyloidogenic proteins function as seeds in amyloid β-protein aggregation

Area of Science:

• Biochemistry
• Neuroscience
• Molecular Biology

Background:

• Amyloid β-protein (Aβ) aggregation is central to Alzheimer's disease (AD) neurodegeneration.
• Proteins can form amyloid fibrils, but cross-seeding effects on Aβ pathways are unclear.
• Exogenous and non-central nervous system (CNS) amyloidogenic proteins may influence Aβ aggregation.

Purpose of the Study:

• To investigate how exogenous and human non-CNS amyloidogenic proteins cross-seed Aβ aggregation.
• To determine the impact of specific protein seeds (casein, fibroin, sericin, actin, islet amyloid polypeptide) on Aβ40 and Aβ42 aggregation.
• To identify Aβ binding sites on these amyloidogenic proteins.

Main Methods:

• Utilized thioflavin T assay to monitor Aβ aggregation kinetics.
• Employed electron microscopy to visualize fibril formation.
• Conducted nuclear magnetic resonance (NMR) spectroscopy to map protein-protein binding sites.

Main Results:

• All tested amyloidogenic protein fibrils acted as cross-seeds for Aβ aggregation.
• Actin showed a stronger cross-seeding effect, while fibroin exhibited a weaker effect.
• NMR identified specific binding interfaces between Aβ and the amyloidogenic proteins.

Conclusions:

• Amyloidogenic proteins, even from dietary or cosmetic sources, can promote Aβ aggregation.
• Binding interactions between Aβ and other amyloid proteins facilitate Aβ aggregation.
• These findings suggest a role for external proteins in the propagation of Aβ amyloidosis.