The Impacts of Gut Bacteroides thetaiotaomicron Exposure on Cognitive Impairment and Aβ Pathology in the 5xFAD Alzheimer’s disease Mouse Model Open Access

Abstract

Alzheimer’s disease (AD), the leading cause of dementia in individuals over 65 years-old, is a neurodegenerative disease characterized by progressive cognitive impairment, the aggregation of amyloid beta (Aβ), and synaptic loss. Alterations of the gut microbiome are present in AD patients, however there are few studies examining the direct effects of the gut microbiome on AD outcomes. The bacterial genus Bacteroides makes up around 50% of the bacteria in the gut microbiome and has been seen to both increase and decrease in individuals with AD depending on the region. This study aimed to investigate the impact of single bacteria within the Bacteroides genera, B. thetaiotaomicron, on cognitive impairment, amyloid pathology, and synaptic markers in male and female wildtype and 5xFAD mice, an amyloid mouse model of AD. Overall, this study demonstrates that B. theta has sex-specific influences on cognitive impairment in 5xFAD mice mediated by increased levels of presynaptic proteins. The protective effect of B. theta in male 5xFAD mice supports the need for additional research to determine the potential therapeutic benefits of B.theta or other members of this bacterial class on AD outcomes.

Table of Contents

Abstract……………………………………………………………………………………………1

Introduction……….……………………………………………………………………………….2

           Alzheimer’s Disease……………………………………………………………………...2

Gut Brain Axis……………………………………………………………………………4

The Gut Microbiome in Patients with AD………………………………………………..6

The Gut Microbiome in AD Mouse Models………………………………………………7

Materials and Methods……………………………………………………………...…………...10

Results……………………………………………………………………………………………16

Discussion………………………………………………………………………………………..22

Future Directions………………………………………………………………………………...26

References………………………………………………………………………………………..28

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, Neuroscience Biology, Cell
Keyword	Alzheimer's disease Microbiome
Committee Chair / Thesis Advisor	Timothy Sampson, Emory University
Committee Members	David Weinshenker, Emory University Ali Cohen, Emory University

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