Award Date

August 2023

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Life Sciences

First Committee Member

Helen Wing

Second Committee Member

Jingchun Chen

Third Committee Member

Eduardo Robleto

Fourth Committee Member

Edwin Oh

Number of Pages

116

Abstract

Alzheimer’s disease (AD) is the leading cause of dementia worldwide, and has become an ever-present problem in aging populations. An increasing body of evidence suggests that neuroinflammation is one of the key drivers of AD pathology. One overlooked contributor to this burden is peripheral inflammation throughout the body. Due to increased permeability of the blood-brain-barrier (BBB) in older age, inflammatory plasma proteins and immune cells infiltrate the CNS and drive neuroinflammation through interactions with neurons and glia. In addition, age-related changes in the composition of gut microbiome taxa lead to increased gut permeability and inflammatory burden. Because inflammatory factors are heritable, a greater understanding of their genetic relationship with AD could identify new biomarkers that contribute to AD pathology or protection against it.Recently, large genome-wide association studies (GWASs) have identified many genetic variants significantly associated with AD, plasma protein levels, and the abundance of gut microbiome taxa. By leveraging these datasets in conjunction with genotyping data from AD patients, our goal was to identify plasma protein levels and gut microbiome taxa that are genetically correlated with AD through analysis of their shared single-nucleotide polymorphisms (SNPs). To accomplish this, we used polygenic risk scores (PRSs) of plasma protein levels and gut microbiome taxa abundance to correlate them and AD through a meta-analysis involving two case/control cohorts. Mendelian Randomization (MR) was used to explore possible causal relationships between plasma protein levels and AD, while linear regression was used to further understand how the APOE gene locus correlates with the genetically-predicted abundance of gut microbiome taxa. Overall, our results identify new candidates of peripheral inflammation that warrant further study in the context of AD pathology.

Keywords

Alzheimer's Disease; Inflammation; Mendelian Randomization; Microbiome; Polygenic Risk Score

Disciplines

Bioinformatics | Genetics | Medical Neurobiology | Neuroscience and Neurobiology | Neurosciences

File Format

pdf

File Size

2950 KB

Degree Grantor

University of Nevada, Las Vegas

Language

English

Rights

IN COPYRIGHT. For more information about this rights statement, please visit http://rightsstatements.org/vocab/InC/1.0/

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