Evaluating the Role of Curli and Gut Escherichia coli Enrichment on Alzheimer’s Disease Outcomes in the 5xFAD Mouse Model Restricted; Files Only

Abstract

Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by the accumulation of amyloid beta (Aβ) plaques and tau neurofibrillary tangles (NFTs) in the brain, leading to cognitive impairment and memory loss. Emerging evidence suggests a potential link between gut microbiome dysbiosis and AD pathogenesis. Several studies have demonstrated elevated gut Enterobacteriaceae levels in AD patients that correlate with increased Aβ pathology. However, the specific mechanisms by which increased Enterobacteriaceae contributes to Aβ pathology remain unclear. Escherichia coli (E. coli), an Enterobacteriaceae species, has drawn attention due to its ability to produce functional amyloid fibers called curli, which have been shown to induce aggregation of human amyloids. Preliminary data from our research lab has shown that gut E. coli enrichment exacerbates cognitive impairment in an AD mouse model, implicating a mechanism by which E. coli worsens AD outcomes. To investigate the necessity of the bacterial amyloid curli for E. coli’s detrimental effects, we compare the effects of gut enrichment with curli-producing K12 E. coli versus a curli-deficient isogenic strain. Importantly, this project aims to elucidate how a specific bacterial species may influence Aβ pathology and cognitive outcomes, ultimately contributing to a deeper understanding of how alterations in the gut microbiome may influence AD pathology and progression.

Table of Contents

Abstract 1

Introduction 2

Alzheimer’s Disease 2

The Gut Microbiome 4

The Gut Microbiome in Alzheimer’s Disease 5

Escherichia coli, Curli, & Amyloid Diseases 6

Materials & Methods 10

Results 14

Discussion & Future Directions 22

References 24

About this Honors Thesis

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School	Emory College
Department	Neuroscience and Behavioral Biology
Degree	B.S.
Submission	Honors Thesis
Language	English
Research Field	Biology, Physiology Biology, Microbiology Biology, Neuroscience
关键词	Escherichia coli 5xFAD Gut microbiome Alzheimer's disease
Committee Chair / Thesis Advisor	Timothy Sampson, Emory University
Committee Members	Steven Sloan, Emory University J. Alex Grizzell, Emory University

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