Alzheimer's Progenitor Amyloid-β Targets and Dissolves Microbial Amyloids and Impairs Biofilm Function

Area of Science:

• Neuroscience
• Microbiology
• Biochemistry

Background:

• Alzheimer's disease (AD) is characterized by amyloid-beta (Aβ) plaques.
• Aβ peptides are also found in the gut, suggesting a gut-brain axis connection.
• Gut opportunistic pathogens like Pseudomonas aeruginosa and Escherichia coli form microbial amyloids (FapC, CsgA).

Purpose of the Study:

• To investigate the interaction between Aβ monomers and microbial amyloids from gut pathogens.
• To explore the potential anti-biofilm and therapeutic implications of Aβ in the gut-brain axis.

Main Methods:

• Utilized a zebrafish model for in vivo imaging of Aβ interaction with microbial amyloids.
• Observed Aβ diffusion into vasculature and localization with FapC/CsgA fibrils.
• Assessed the effects of Aβ-modified microbial fibrils (Faβ) on neuronal and intestinal cell lines.

Main Results:

• Aβ monomers disintegrate FapC and CsgA microbial amyloids.
• Aβ-modified FapC (Faβ) shows selective toxicity to neuronal cells but is phagocytosed by intestinal cells.
• Microbial fibrils lose cell adhesion properties and detach from cell membranes after Aβ interaction.

Conclusions:

• Aβ monomers exhibit an anti-biofilm activity against gut pathogens.
• This interaction suggests a novel role for Aβ in modulating the gut microbiome.
• Findings support the development of Aβ-based therapeutics for Alzheimer's disease and infections.