Cryo-EM Observation of AA Amyloid Fibrils in Mouse Model of Systemic AApoAII Amyloidosis

Area of Science:

• Biochemistry
• Structural Biology
• Neuroscience

Background:

• Protein misfolding diseases are linked to amyloid fibril formation.
• Co-deposition of different amyloid fibrils is increasingly relevant.
• Serum amyloid A (SAA) protein is implicated in amyloidosis.

Purpose of the Study:

• To determine the structures of SAA protein-derived amyloid fibril morphologies.
• To investigate SAA fibril structures in a mouse model typically associated with other amyloid types.
• To compare SAA fibril structures across different contexts.

Main Methods:

• Cryo-electron microscopy (cryo-EM) was used to determine fibril structures.
• Amyloid fibrils were extracted from a specific mouse strain.
• Structural analysis focused on protomer conformation and fibril stacking.

Main Results:

• Two distinct SAA protein-derived amyloid fibril morphologies were identified.
• The protomer conformation was consistent with previously reported ex vivo SAA fibrils.
• A different relative arrangement of fibril protein stacks was observed compared to prior studies.

Conclusions:

• SAA-derived amyloid fibrils exhibit conserved protein folds across different mouse strains.
• The fibril structure remains consistent regardless of the disease context.
• These findings contribute to understanding amyloid fibril diversity in protein misfolding diseases.