Accelerated Amyloid Beta Pathogenesis by Bacterial Amyloid FapC

Area of Science:

• Microbiology
• Neuroscience
• Biochemistry
• Molecular Biology

Background:

• The gut-brain axis is increasingly recognized for its role in neurological health and disease.
• Amyloid beta (Aβ) aggregation is a hallmark of Alzheimer's disease (AD).
• Gut microbiome dysbiosis and infections are implicated in neurodegenerative conditions.

Purpose of the Study:

• To investigate the role of *Pseudomonas aeruginosa* FapC amyloid fragments (FapCS) in seeding Aβ aggregation.
• To elucidate the structural changes and functional consequences of bacterial cross-seeding of Aβ.
• To explore potential therapeutic targets and biomarkers related to bacterial influence on Aβ pathology.

Main Methods:

• In vitro seeding assays using FapCS and Aβ peptides.
• Structural analysis of Aβ fibrils using techniques like cryo-electron microscopy (implied by periodicity and diameter changes).
• Zebrafish models to assess behavioral and cognitive impairments following exposure to bacterial fragments and Aβ.

Main Results:

• FapCS effectively bind and catalytically seed Aβ amyloidosis.
• Seeded Aβ fibrils exhibit altered structural characteristics: shortened periodicity and increased diameter (37% rise).
• Exposure to FapCS and *P. aeruginosa* biofilm fragments induced behavioral pathology, immunohistological changes, and cognitive deficits in zebrafish.

Conclusions:

• Provides the first evidence of structural integration and inheritance in peptide cross-seeding between bacterial amyloids and Aβ.
• Highlights the catalytic role of infectious bacteria in promoting Aβ amyloidosis, suggesting a link between gut infections and AD.
• Identifies potential therapeutic strategies targeting bacterial influence on amyloidogenesis and proposes altered Aβ fibril signatures as biomarkers.