Identifying Polymorphs of Amyloid-β (1-40) Fibrils Using High-Resolution Atomic Force Microscopy

Area of Science:

• Biochemistry
• Biophysics
• Neuroscience

Background:

• Amyloid-β (Aβ) fibrils are polymorphic, with morphology influenced by formation conditions.
• Understanding Aβ fibril structure is crucial for neurodegenerative disease research.

Purpose of the Study:

• To apply high-resolution atomic force microscopy (HR-AFM) and volume-per-length analysis for characterizing polymorphic Aβ fibril preparations.
• To define, identify, and quantify the structural components of these fibrils.

Main Methods:

• Utilized HR-AFM for high-resolution imaging of Aβ fibril preparations.
• Applied volume-per-length analysis to quantify fibril structural components.
• Confirmed composition of discrete cross-β filaments.

Main Results:

• HR-AFM analysis, combined with volume-per-length measurements, successfully characterized polymorphic Aβ fibril structures.
• Determined the number of striations within individual fibrils.
• Demonstrated narrower distribution data compared to electron microscopy mass-per-length analysis.

Conclusions:

• HR-AFM with volume-per-length analysis provides a rapid, label-free, and quantitative method for Aβ fibril morphological characterization.
• This technique enhances the understanding of Aβ fibril polymorphism.
• Facilitates precise structural definition of amyloid fibrils.