Medicine and Health Sciences Commons^™

The Role Of Apolipoprotein E In Regulating Tau Pathogenesis And Neurodegeneration In A Tauopathy Mouse Model, Yang Shi

Arts & Sciences Electronic Theses and Dissertations

APOE4 is the strongest genetic risk factor for late-onset Alzheimer's disease (AD). APOE4 increases brain amyloid-β (Aβ) pathology relative to other APOE isoforms. However, whether APOE independently influences tau pathology, the other pathological hallmark of AD and other tauopathies, or tau-mediated neurodegeneration, is not clear. By generating P301S tau transgenic mice on either a human APOE knock in (KI) or APOE knockout (KO) background, we show that the presence of human APOE, regardless of APOE isoforms, leads to various degrees of brain atrophy in 9-month old P301S mice, whereas APOE ablation strongly protects against neurodegeneration. In particular, P301S/E4 mice develop …

Cyclophilin 40 As A Novel Disaggregase, Jeremy Dustin Baker

USF Tampa Graduate Theses and Dissertations

The negative health and economic impacts of neurodegenerative diseases on Americans is astounding and accelerating with an aging population. The Alzheimer’s Association reports that 5.7 million Americans suffer from Alzheimer’s disease (AD), a number which is expected to increase to 14 million by 2050. In economic terms, AD and other neurodegenerative disorders will cost the US over $275 billion in 2018, rising to over $1 trillion annually by 2050. AD causes gross brain atrophy and is most damaging throughout the cortex and the hippocampus, regions required for higher cognitive function and memory. AD presents as tangles within neurons composed of …

Proteolysis Of Cx3cl1 Impacts Cx3cr1 Signaling And Therapeutic Benefits In A Tauopathy Model, Dylan John Finneran

USF Tampa Graduate Theses and Dissertations

Alzheimer’s disease (AD) is a progressive, neurodegenerative disorder and the most common form of dementia. The hallmark pathologies of AD are extracellular aggregates of amyloid-beta, intracellular aggregates of microtubule associated protein tau and increased neuroinflammation. Current therapeutics offer only symptomatic relief and clinical trials investigating therapeutic benefits of non-steroidal anti-inflammatory drugs have yielded no positive results. Therefore, recent work has focused on immunomodulators, such as CD200 and fractalkine, as potential therapeutic targets for AD.

Fractalkine (CX3CL1; FKN) is expressed as a transmembrane protein with an N-terminal chemokine domain followed by a long, mucin-like stalk. FKN can signal as a membrane-bound …

The Comparison Of Effective Education Methods To Increase Knowledge About Alzheimer's Disease., Lillian M. Kopsolias

College of Arts & Sciences Senior Honors Theses

Alzheimer’s disease (AD) is a disease most people recognize, but have many misconceptions about. One way to decrease the amount of misconceptions about AD is to educate the general public on the disease. Many educational methods, such as person-centered care education, have been researched, but none have focused on the general public. Therefore, the purpose of this study is to compare two educational methods used today, reading a passage from a reliable online source (traditional educational method) and watching documentaries (person-centered care educational method), to find if a specific way of presenting them will prove efficient for Alzheimer’s education. The …

Targeting The Hsp90/Aha1 Complex For The Treatment Of Tauopathies, Lindsey Brooke Shelton

USF Tampa Graduate Theses and Dissertations

The microtubule associated protein, tau, is involved in regulating microtubule stability and axonal transport. When tau becomes hyperphosphorylated it can disassociate from the microtubules and start to aggregate. These tau aggregates are the hallmarks of many diseases known as tauopathies. The heat shock protein 90 kDa (Hsp90) chaperone network is highly involved in modulating client proteins, including tau. However, during aging and disease the Hsp90 chaperone network becomes highly imbalanced with some Hsp90/co-chaperone complexes increasing, while others are repressed. This imbalance in Hsp90/co-chaperone complexes could result in a worsening of tau pathology in Alzheimer’s disease.

Hsp90 inhibition has been of …

The Famous Names Discrimination Task As A Biomarker Of Alzheimer's Disease Risk: An Erp Study, Elizabeth Rose Paitel

Master's Theses (2009 -)

Current ERP research emphasizes age- and pathology-related declines in neural processing in the form of attenuated amplitudes and prolonged latencies. Notably, there is a gap in the ERP literature regarding neural processing trajectories in the time between healthy young adulthood and clinical MCI/AD samples. fMRI research, however, has demonstrated periods of increased, compensatory activation in healthy, cognitively intact APOE ɛ4 carriers both during resting state and event-related tasks (Bondi, Houston, Eyler, & Brown, 2005; Evans et al., 2014; Filippini et al., 2009; Rao et al., 2015), consistent with compensatory theories of cognitive aging (Cabeza, 2002; Park & Reuter-Lorenz, 2009; Reuter-Lorenz …

Factors Influencing Alzheimer's Disease Healthcare Utilization Patterns In Puerto Rico, Carlamarie Noboa

Walden Dissertations and Doctoral Studies

Alzheimer's disease (AD) is associated with substantial healthcare utilization costs, resulting in a public health priority. In this study, the relationship between the demographic characteristics of age, gender, and type of health insurance; the presence of comorbidities of older Puerto Rican residents diagnosed with AD; and their healthcare utilization patterns (i.e., medical office and emergency room visits and hospital admissions) was examined using Andersen's behavioral model. Data from the 2013 Puerto Rico Health Study was used in this retrospective cohort design study. All AD cases aged -?¥ 60 years were extracted using systematic random sampling. One-way ANOVA-WELCH, Mann-Whitney U test, …

A Story To Tell Among Minority Alzheimer's Patient Caregivers: A Phenomenological Study, Albertina Lashonda Walker

Walden Dissertations and Doctoral Studies

The level of burden experienced by caregivers of patients diagnosed with Alzheimer's disease is high. Studies that examine this burden by taking into account cultural and spiritual differences are limited, particularly with regard to minority populations. The purpose of this study was to investigate the burden and challenges faced by minority caregivers providing in-home care to Alzheimer's patients. Guided by social support theory, a phenomenological study design was used with semi-structured interviews of 12 caregivers to examine their perspectives on the burden and challenges they face, including their lived experiences, cultural and spiritual values, and interaction with health professionals. Thematic …

Pathological Changes In Hippocampal Synaptic Transmission And Neuronal Function During Early Disease In The Novel Tgf344-Ad Rat Model, Lindsey Allyson Smith

All ETDs from UAB

Alzheimer’s disease (AD) is the leading cause of dementia in those 65 years and older and the 6th leading cause of death in the United Sates. Current treatments only target symptoms of the disease and cannot slow or halt disease progression. The novel and comprehensive TgF344-AD rodent model may bridge the translational gap previous animal models have failed to traverse by providing the platform to probe pre-lesion synapse dysfunction, which is thought to result primarily from increased levels of toxic soluble amyloid beta and hyperphosphorylated tau. The most recently developed model, the TgF344-AD rat was created in 2013 by insertion …