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

Syed Aoun Ali, Ka Hang Karen Chung, Helen Forgham, William P Olsen, Aleksandr Kakinen, Arunpandian Balaji, Daniel E Otzen*, Thomas Paul Davis*, Ibrahim Javed*

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Abstract

Alzheimer's disease (AD) is a leading form of dementia where the presence of extra-neuronal plaques of Amyloid-β (Aβ) is a pathological hallmark. However, Aβ peptide is also observed in the intestinal tissues of AD patients and animal models. In this study, it is reported that Aβ monomers can target and disintegrate microbial amyloids of FapC and CsgA formed by opportunistic gut pathogens, Pseudomonas aeruginosa and Escherichia coli, explaining a potential role of Aβ in the gut-brain axis. Employing a zebrafish-based transparent in vivo system and whole-mount live-imaging, Aβ is observed to diffuse into the vasculature and subsequently localize with FapC or CsgA fibrils that were injected into the tail muscles of the fish. FapC aggregates, produced after Aβ treatment (Faβ), present selective toxicity to SH-SY5Y neuronal cells while the intestinal Caco-2 cells are shown to phagocytose Faβ in a non-toxic cellular process. After remodeling by Aβ, microbial fibrils lose their native function of cell adhesion with intestinal Caco-2 cells and Aβ dissolves and detaches the microbial fibrils already attached to the cell membrane. Taken together, this study strongly indicates an anti-biofilm role for Aβ monomers that can help aid in the future development of selective anti-Alzheimer's and anti-infective medicine.

Original languageEnglish
Article numbere2301423
JournalAdvanced Science
Volume10
Issue29
Number of pages16
ISSN2198-3844
DOIs
Publication statusPublished - Oct 2023

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