Exploring the Aβ_1-42 fibrillogenesis timeline by atomic force microscopy and surface enhanced Raman spectroscopy

Area of Science:

• Neuroscience
• Biochemistry
• Materials Science

Background:

• Alzheimer's disease (AD) is a leading cause of dementia, characterized by amyloid-β (Aβ) plaques.
• The precise mechanisms driving Aβ aggregation and neurotoxicity remain incompletely understood.
• Investigating early Aβ aggregation is crucial for developing effective AD therapies.

Purpose of the Study:

• To characterize the morphological and structural changes during Aβ₁₋₄₂ fibrillogenesis.
• To determine the timeline of Aβ₁₋₄₂ assembly formation up to 48 hours.
• To identify key structural transitions indicative of early-stage aggregation.

Main Methods:

• Atomic Force Microscopy (AFM) for morphological analysis of Aβ₁₋₄₂ aggregates.
• Surface-Enhanced Raman Spectroscopy (SERS) for chemo-structural characterization.
• Incubation of Aβ₁₋₄₂ for up to 48 hours to capture aggregation dynamics.

Main Results:

• AFM revealed characteristic protofibrils and macromolecular networks forming over time.
• SERS tracked secondary structure variations, showing the transition to β-sheet dominance.
• Early aggregation stages were characterized by distinct protofibril formation and structural changes.

Conclusions:

• Understanding early Aβ₁₋₄₂ fibrillogenesis is vital for elucidating AD pathophysiology.
• Identifying early aggregation intermediates can reveal potential therapeutic targets.
• This study provides a timeline and structural insights into the initial steps of Aβ aggregation.