Medicine and Health Sciences Commons^™

Cis-Regulatory Elements: Relevance For Alzheimer's Disease, Brianne Brazell Rogers

All ETDs from UAB

Alzheimer’s disease (AD) is the most common neurodegenerative disease, currently affecting more than six million Americans with limited treatment options. Identifying genetics contributors to neurodegenerative diseases has contributed critical insights into potential disease mechanisms. The majority of disease-associated genetic variants are located in non-coding regions, likely in regulatory elements, and affect the expression of target genes whose function contributes to neurodegeneration. Here, I performed a case-control study utilizing nuclei from dorsolateral prefrontal cortex postmortem tissue to correlate chromatin accessibility with gene expression and nominate 40,831 AD-specific candidate cis-regulatory elements. Additionally, work in this dissertation nominates ZEB1 and MAFB as candidate …

Investigating A Multimodal Approach To Clinical Diagnosis Of Mild Cognitive Impairment And Alzheimer’S Disease, Sean M. Flannery

Psychology Theses & Dissertations

An estimated 5.8 million Americans suffer from dementia due to Alzheimer’s disease (AD), with that number projected to grow to 13.8 million by mid-century (Alzheimer’s Association, 2019). Mild cognitive impairment (MCI) describes the stage between normal cognitive decline that comes with aging and a dementia diagnosis (Peterson, 1999). Due to a lack of a cure or particularly effective treatment, a major goal of treatment is to focus on improving quality of life (Budson & Solomon, 2016). An early and accurate diagnosis can address this goal in a variety of ways. Despite the high prevalence and immense amount of research in …

A Model Of Agitated Behavioral Symptoms In Persons With Alzheimer Disease, Katherine Kero

Wayne State University Dissertations

Background: Worldwide population trends are shifting with the population of Elders expected to dramatically increase in absolute and relative numbers in coming years. Alzheimer Disease (AD) is a common and costly disease of aging with agitation being the most poorly managed and detrimental behavioral symptom of the condition. The Nursing Theory of Unpleasant Symptoms provides a conceptual basis for understanding agitated behavioral symptoms associated with AD in the context of its antecedent causes and outcomes of the symptoms.

Purpose: The purpose of this dissertation was to model the predictors and outcomes of agitated behavioral symptoms in persons with AD. The …

Network Exploration Of Correlated Multivariate Protein Data For Alzheimer's Disease Association, Matthew J. Lane

Theses

Alzheimer Disease (AD) is difficult to diagnose by using genetic testing or other traditional methods. Unlike diseases with simple genetic risk components, there exists no single marker determining as to whether someone will develop AD. Furthermore, AD is highly heterogeneous and different subgroups of individuals develop the disease due to differing factors. Traditional diagnostic methods using perceivable cognitive deficiencies are often too little too late due to the brain having suffered damage from decades of disease progression. In order to observe AD at early stages prior to the observation of cognitive deficiencies, biomarkers with greater accuracy are required. By using …

Forget-Me-Not, Daniel Barber-Cironi, Shawn Nicholson, Jake Kruse, Nicole Dent

Williams Honors College, Honors Research Projects

The purpose of Forget-Me-Not is to provide another level of care and comfort to those suffering from mild dementia, as well as provide further assistance for a friend, family member, or caretaker who may look after them. Research shows that timely reminders and persistent information can greatly improve the quality of life for those afflicted with mild dementia (Mokhtari et al.). Forget-Me-Not’s persistent display and wearable smart-bracelet offer a customizable and well connected system to provide these reminders. For the caretaker, a mobile application is provided in order to maintain the display and notify them of emergencies or critical events …

Impairment Of The Gliovascular Unit In Neurological Disease, Ian Kimbrough

All ETDs from UAB

Cerebral blood flow is regulated by vasoactive molecules released by astroglial cell processes that ensheath the entire cerebrovasculature. This regulation of blood flow in response to neuronal activity is a process known as functional hyperemia. Astrocytes, along with their associated neurons and microvessels, are organized into a functional system called the gliovascular unit (GVU). The astroglial component of the GVU is integral in both regulation of blood flow and maintenance of the blood-brain barrier (BBB). In disease, this system can be disrupted. We found that glioma cells displace astrocytic processes, called endfeet, and prevent their communication with associated vessels, leading …

Correlation Of Amyloid Beta And Spatial Learning And Memory Deficits On A Thy1-App Mouse Model For Alzheimer's Disease, Amber Lynn Betz

Theses and Dissertations - UTB/UTPA

The McGill-Thy1 APP mouse is a triple transgenic model of Alzheimer disease, which has the mutant amyloid precursor protein to synergistically over-produce amyloid beta plaques. These mice exhibit visuo-spatial learning impairment at 3 months of age and memory impairment at 10-13 months of age in the Morris water maze. To extend these findings mice at 3, 5, and 7 months of age were tested on the Barnes maze. Non-Transgenic and Transgenic mice showed improvement during acquisition. However, 3 month and 5 month McGill Thy1- APP mice showed impaired acquisition learning while 7 month showed a learning and memory deficit compared …

Tau-Sh3 Interactions: Implications For Alzheimer's Disease, Jesse Nicholas Cochran

All ETDs from UAB

Alzheimer’s disease (AD) is the most common neurodegenerative disease and with Americans’ increasing longevity it is becoming an epidemic. There are currently no effective treatments for this disorder. Abnormalities of tau track more closely with cognitive decline than the most studied therapeutic target in AD, amyloid-beta, but the optimal strategy for targeting tau has not yet been identified. Based on considerable preclinical data from AD models, we hypothesize that interactions between tau and SH3 domain–containing proteins are pathogenic in AD. Genetically reducing either tau or tau interactants has beneficial effects relevant to AD. Here, we describe a drug screen for …

The Role Of Post-Translational Modifications And Valosin-Containing Protein In The Turnover And Stability Of The Microtubule-Associated Protein Tau, Philip James Dolan

All ETDs from UAB

Alzheimer Disease (AD) is pathologically characterized by the appearance of senile plaques composed of ß-amyloid and neurofibrillary tangles composed of the microtubule-associated protein tau. During the development of AD pathology, tau is hyperphosphorylated and aberrantly cleaved, both of which potentially contribute to its pathogenic and fibrillogenic nature. The accumulative nature of these post-translational products, and their contribution to tau pathology, has led to a great deal of study regarding mechanisms for both the maintenance of tau stability and degradation. The first part of this study reviews the developments regarding the contribution of phosphorylated tau to different physiological and pathological processes. …

The Effects Of Psychotropic Medication Therapy On The Behaviors Of The Institutionalized Alzheimer's Disease Patient, Mary Beth Mckinneu

MSN Research Projects

Alzheimer's disease is a devastating illness that is common among the nursing home population. Treatment for Alzheimer's disease is usually palliative and consists of using psychotropic medications to control aggressive and agitated behaviors exhibited by its victims. The purpose of this descriptive study was to identify behaviors exhibited by Alzheimer's disease patients before and after receiving psychotropic medications. Johnson's Behavioral System Model was used as the theoretical framework for this study. The sample (N = 33) consisted of nursing home residents with a diagnosis of Alzheimer's disease who were treated with one psychotropic medication. The researcher used chart review to …