Author ORCID Identifier
https://orcid.org/0009-0008-1505-9888
Date Available
12-5-2024
Year of Publication
2024
Document Type
Doctoral Dissertation
Degree Name
Doctor of Philosophy (PhD)
College
Medicine
Department/School/Program
Pharmacology and Nutritional Sciences
Advisor
Dr. Ai-Ling Lin
Abstract
Apolipoprotein E4 allele (APOE4) carriers show early metabolic changes, heightening the genetic risk of late-onset Alzheimer's Disease (AD), characterized by amyloid-β and tau tangle plaques and neurodegeneration. Its development is influenced by age, environment, and genetics, with Mild Cognitive Impairment (MCI) often preceding AD, providing a crucial window for early intervention. Factors in AD progression include sex differences and gut microbiome imbalances, with women disproportionately affected and APOE4 carriers showing early metabolic and cognitive changes. This study explores the potential of prebiotic inulin, probiotic Bifidobacterium animalis, and fecal microbiota transplants (FMT) from healthy donors to mitigate AD risks by modulating gut microbiota and enhancing metabolic functions in APOE4 mice. We hypothesize that these interventions will improve gut microbiome composition and metabolic functions, thus reducing AD risk in APOE4 mice. Our results show that inulin supplementation restored gut microbial diversity and reduced inflammation-associated pathways, with sex-specific effects. B. animalis altered microbial composition and elevated metabolites related to energy and neurotransmission. FMT from healthy donors improved glucose tolerance, reduced anxiety, enhanced cerebral blood flow, and modulated metabolic pathways. Healthy-FMT male mice had the lowest hippocampal amyloid-β accumulation, while female mice exhibited improved neurotransmitter synthesis. These findings highlight the potential of microbiome-based therapies for improving gut health and metabolic functions in APOE4 mice, offering a foundation for personalized interventions in neurodegenerative disorders.
Digital Object Identifier (DOI)
https://doi.org/10.13023/etd.2024.500
Funding Information
This study was supported by the National Institutes of Health Grant (no.: RF1AG062480) in 2019.
Recommended Citation
Chang, Ya-Hsuan, "MITIGATING RISKS FOR DEMENTIA IN APOE4 MICE: EFFICACY OF PREBIOTIC INULIN, PROBIOTICS, AND FECAL MICROBIOTA TRANSPLANTS" (2024). Theses and Dissertations--Pharmacology and Nutritional Sciences. 61.
https://uknowledge.uky.edu/pharmacol_etds/61
