Assessing amyloid fibrils and amorphous aggregates: A review

Area of Science:

• Biochemistry and Molecular Biology
• Neuroscience
• Biophysical Chemistry

Background:

• Protein misfolding and aggregation are key drivers in neurodegenerative diseases.
• Aggregates appear as amyloid fibrils or amorphous structures, impacting disease mechanisms.
• Understanding aggregate structure and behavior is vital for therapeutic development.

Purpose of the Study:

• To provide a comprehensive overview of techniques for detecting and characterizing protein aggregates.
• To integrate conventional and advanced methods for studying aggregate formation and structure.
• To critically evaluate the capabilities and limitations of various analytical approaches.

Main Methods:

• Spectroscopic and spectrometric tools (fluorescence, Raman, mass spectrometry) for identification.
• Microscopy techniques (AFM, electron microscopy) for morphological analysis.
• In situ detection, separation methods, X-ray diffraction, and computational approaches (AI).

Main Results:

• The review systematically categorizes and describes diverse analytical techniques.
• It highlights the utility of spectroscopic, microscopic, and separation methods.
• Emerging computational and AI-driven approaches are emphasized for predicting aggregation.

Conclusions:

• A wide array of methods exists for protein aggregate analysis, each with strengths and weaknesses.
• Integrated approaches combining multiple techniques offer a more complete understanding.
• This review serves as a practical resource for researchers in neurodegeneration and protein aggregation.