Medicine and Health Sciences Commons^™

Apoe Genotype And Sex Modulate Ketogenic Diet Enhancements To Metabolism And Gut Microbiome In Young Mice, Andrew T. Yackzan

Theses and Dissertations--Medical Sciences

The apolipoprotein ε (APOE) allele in humans has been associated with risk for development of Alzheimer’s disease (AD). There are predominately three variations of the allele – ε2 (E2), ε3 (E3), and ε4 (E4) – with E4 contributing the greatest risk of AD development. Recent research has unveiled evidence of neurometabolic and neurovascular deficits in E4 carriers present decades before the onset of dementia; it is believed these chronic defects play a major role in the development of AD, thus making them a potential target for preventative intervention. The purpose of this study was to examine the effect of a …

Efficacy Of Prebiotic Dietary Intervention To Mitigate Risks For Dementia Via The Gut-Brain Axis, Lucille M. Yanckello

Theses and Dissertations--Pharmacology and Nutritional Sciences

Alzheimer’s disease (AD) is the most common form of dementia with various risk factors including age, environmental factors such as brain injury and genetic factors, such as the E4 allele of the Apolipoprotein gene. Presence of the APOE4 allele increases AD risk by two- to four- fold. Recent studies have shown that mild traumatic brain injury (mTBI), even without loss of consciousness, increases risk of dementia diagnosis by more than two-fold in military personnel and is also a significant environmental risk factor for developing dementia in the general population. The gut-brain axis (GBA) or bi-directional communication between the brain and …

Evaluating The Relationship Between Plasma Biomarkers And Dementia Using Hierarchical Clustering Analysis And Linear Modeling, Zachary Winder

Theses and Dissertations--Physiology

Dementia is a disorder characterized by a significant decline from baseline in one or more cognitive domains that interferes with independence. Prevalence of dementia worldwide is estimated at 50 million people, with that number expected to triple by 2030, coming with a cost of roughly $2 trillion. Clinically, dementia is diagnosed using cognitive evaluations, with varying domains affected and to different degrees depending on the underlying pathology and stage of disease. Alzheimer’s disease (AD) and vascular contributions to cognitive impairment and dementia (VCID) are the two leading causes of dementia, and both have pathologies which can be visualized using MRI. …

Multiple Proteinopathies And Their Role In Cognitive Impairment And Neurodegenerative Diseases, Shama D. Karanth

Theses and Dissertations--Epidemiology and Biostatistics

Most age-related neurodegenerative disorders are associated with the aggregation of misfolded and aberrant proteins. Alzheimer’s disease (AD) is one of the most common neurodegenerative disorders and is highly prevalent in older adults. Neuropathologically, AD is characterized by the accumulation of amyloid-β (Aβ) plaques and neurofibrillary tangles (NFTs). Other misfolded proteins, including α-synuclein and transactive response DNA-binding protein 43 (TDP-43), are also commonly observed in aged brains. Aberrant α-synuclein has been associated with Parkinson's disease, Dementia with Lewy bodies, and multiple system atrophy, whereas TDP-43 has been associated with multiple neurological diseases, the most common of which was designated as limbic-predominant, …

Preclinical Targeting Of Trem2 For The Treatment Of Alzheimer's Disease-Type Pathology In A Transgenic Mouse Model, Brittani Rae Price

Theses and Dissertations--Physiology

Alzheimer's disease (AD) is defined as a progressive neurodegenerative disorder and is characterized by a devastating mental decline. There are three pathological hallmarks of the disease necessary for its diagnosis, these are extracellular amyloid plaques comprised of the beta-amyloid (Aβ) protein, intracellular neurofibrillary tangles comprised of hyperphosphorylated tau protein, and marked neuronal loss. Active immunization against Aβ_1-42 or passive immunization with monoclonal anti-Aβ antibodies has been shown to reduce amyloid deposition and improve cognition in transgenic mouse models of AD, aged beagles, and nonhuman primates. Unfortunately, due to cerebrovascular adverse events, both active and passive immunization strategies targeting Aβ …

The Prebiotic Inulin Beneficially Modulates The Gut-Brain Axis By Enhancing Metabolism In An Apoe4 Mouse Model, Jared D. Hoffman

Theses and Dissertations--Pharmacology and Nutritional Sciences

Alzheimer’s disease (AD) is the most common form of dementia and a growing disease burden that has seen pharmacological interventions primarily fail. Instead, it has been suggested that preventative measures such as a healthy diet may be the best way in preventing AD. Prebiotics are one such potential measure and are fermented into metabolites by the gut microbiota and acting as gut-brain axis components, beneficially impact the brain. However, the impact of prebiotics in AD prevention is unknown. Here we show that the prebiotic inulin increased multiple gut-brain axis components such as scyllo-inositol and short chain fatty acids in the …

Explorations In Homeoviscous Adaptation And Mass Spectral Analysis Of Membrane Lipids, Michael Douglas Timmons

University of Kentucky Doctoral Dissertations

The focus of this dissertation is centered on the mass spectral analysis of lipids and changes occurring in keeping with the concept of homeoviscous adaptation [1]. Homeoviscous adaptation is the process of modification of membrane lipids in response to environmental stimuli [1]. Dissertation investigations applied this concept to prokaryotic and eukaryotic organisms, and expanded the perception of environmental factors from exogenous organic solvents to intracellular environment.

The field of lipidomics deals with the analysis of phospholipid and fatty acid components of membranes the changes that occur due to environmental stimuli and their biological significance [2-6]. The high sensitivity of mass …