Engineering Commons^™

Detecting Physiological Concentrations Of Alzheimer’S Associated Amyloid-Β Protein Utilizing A Cell-Based Response, Brittany Elizabeth Watson

Theses and Dissertations

Alzheimer’s disease (AD) is characterized symptoms of cognitive impairment resulting from blood-brain barrier (BBB) breakdown and neuronal cell death. AD is associated with aggregated amyloid-β (Aβ) plaques deposited around brain vasculature and within the brain. Changes in the brain occur up to 20 years before symptoms arise; however, there is currently no pre-symptomatic detection method available for AD. An intact BBB requires tight junction proteins (TJs) that render relatively high transendothelial electrical resistance (TEER). AD-associated breakdown of the BBB correlates with vascular Aβ deposition, suggesting that aggregated, pathological Aβ can modulate TEER. We explore leveraging this cellular response for early …

Brain Morphometry From Neuroimaging As A Biomarker For Alzheimer's Disease, Nonyelum Benedicta Aniebo

Browse all Theses and Dissertations

Alzheimer’s disease (AD) is the seventh leading cause of death globally with an estimated 6.5 million Americans aged 65 and above living with Alzheimer’s dementia in 2022 and at a projected national cost of $321 billion. AD is characterized by a progressive and irreversible neurodegenerative dysfunction with clinical symptoms such as deterioration in cognition and memory loss. The Alzheimer’s Disease Neuroimaging Initiative (ADNI) is a multi-site, public-private global research initiative that supports both investigation and development of treatments that slow or terminate AD progression. The study included 60 participants, comprising 30 AD and 30 control cohorts respectively. All participants were …

Focused Ultrasound-Enabled Blood-Based Liquid Biopsy (Sonobiopsy) For Brain Disease Diagnosis, Christopher Pham Pacia

McKelvey School of Engineering Theses & Dissertations

Brain cancer severely threatens human health due to its disruption of neurological function, poor prognosis, and substantial reduction in quality of life. Glioblastoma (GBM) is the most devastating brain cancer; not only is it the most common malignant primary tumor in adults, but also it has a median survival of 14 months with a 5-year survival rate of less than 5%. Despite advances in multidisciplinary treatment that includes surgical resection, radiation therapy, and chemotherapy, almost all patients experience tumor progression and nearly universal mortality within 2 years. However, advances in patient care have suggested that the accurate diagnosis of molecular …

Comparison Of Longitudinal Changes In Resting State Functional Magnetic Resonance Imaging Between Alzheimer’S And Healthy Controls, Berk Can Yilmaz

Theses

Resting State Functional Magnetic Resonance Imaging (rs-fMRI) is a technique that is widely used for analyzing brain function using different approaches and methods. This study involves rs-fMRI analysis of Blood Oxygenation Level Dependent (BOLD) signals acquired from Alzheimer’s disease (AD) Patients and Healthy Controls (HC). Each subject in the study had both functional and anatomical images with at least one rs-fMRI scan with their Anatomical (T1) scans. Previous rs-fMRI studies have demonstrated that AD shows differences in Amplitude of Low Frequency (<0.1 Hz) Fluctuations (ALFF), and Regional Homogeneity (ReHo) measures according to HCs.

The aim of the study is to investigate individual and group level differences using ReHo and mALFF related …

Computational Investigation Of The Interactions Between Bioactive Compounds And Biological Assemblies, Tye D. Martin

Biomedical Engineering ETDs

Small, biologically active molecules with unique properties and applications are potential solutions to a wide range of threats to global health including infectious agents and neurodegenerative disease. Experimental studies on a class of oligomeric p-phenylene ethynylenes (OPEs) have shown potential both as bioactive antimicrobials and fluorescent sensing agents for tracking amyloid-β (Aβ) aggregates found in Alzheimer’s Disease (AD). A second type of small molecule with potential applications in AD therapy, curcumin, has been found to interfere with Aβ fibril growth. Curcumin also attenuates Aβ-membrane interactions and Aβ toxicity. Our goal has been to use computational techniques to better understand the …

Capillary Electrophoresis For Analysis Of Aβ1-42 Adsorption And Photo-Crosslinking, Jennifer Lynn Kurtz

Graduate Theses and Dissertations

The accumulation of amyloid-beta (Aβ) oligomers is believed to be the driving force behind Alzheimer’s disease (AD) pathogenesis. Due to the metastable nature of Aβ oligomers, the knowledge of Aβ aggregation and accumulation is not well understood. Here, we use capillary electrophoresis (CE) and photo-induced crosslinking of unmodified proteins (PICUP) to learn about the aggregation of Aβ.

First, we explore the effect of capillary coating on Aβ1-42 protein loss using CE. The dynamic coatings tested were PHEA and 50 kDa, 2000 kDa, 5000 kDa, and 8000 kDa PEO. The covalent coating tested was PVA. The results indicated that 2000 kDa …

Dynamic Complexity And Causality Analysis Of Scalp Eeg For Detection Of Cognitive Deficits, Joseph Curtis Mcbride

Doctoral Dissertations

This dissertation explores the potential of scalp electroencephalography (EEG) for the detection and evaluation of neurological deficits due to moderate/severe traumatic brain injury (TBI), mild cognitive impairment (MCI), and early Alzheimer’s disease (AD). Neurological disorders often cannot be accurately diagnosed without the use of advanced imaging modalities such as computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET). Non-quantitative task-based examinations are also used. None of these techniques, however, are typically performed in the primary care setting. Furthermore, the time and expense involved often deters physicians from performing them, leading to potential worse prognoses for patients.

If …

Discovery And Characterization Of Multi-Target Directed Ligands As Inhibitors Of Amyloid-Β Aggregation And Regulators Of Alzheimer's Disease, Jui-Heng Tseng

Theses and Dissertations

Alzheimer's disease (AD) is the most common neurodegenerative disease in the world. As the disease advances, symptoms include confusion, language skill breakdown, and long term memory loss - and culminate in death. Existing therapies for AD provide symptomatic benefits but cannot halt or slow the disease pathogenesis.

Increasing evidence reveals the multi-factorial nature of AD. Numerous factors, including amyloid-β (Aβ) aggregation, calcium homeostasis dysregulation, and oxidative stress, contribute to disease development and interplay with each other. Therefore, multi-target directed ligands (MTDLs) may present an effective AD treatment. Among all factors, Aβ aggregation is suggested to play the most crucial role. …

Quantitation And Identification Of Protein S-Nitrosylation: Implication For The Progression Of Alzheimer's Disease, Siyang Wang

Doctoral Dissertations

Protein S-nitrosylation, the covalent modification of a cysteine sulfhydryl group by nitric oxide (NO), plays a critical role in post-translational modification (PTM) that regulates a large variety of cellular functions and signalling events. The nitrosylation state changes with oxidative damage and is involved in variety of cancers and neurodegeneration diseases.

Three technologies were developed for nitrosylated protein detection and identification. Capillary gel electrophoresis with laser induced fluorescence (CGE-LIF) detection was used for the detection and quantitation of nitrosylated proteins. A two-dimensional micro-electrophoresis (2D μ-CE) separations system was also built to detect nitrosylated proteins via poly (methylmethacrylate) microchips. Proteomics following nitrosylated …

The Contribution Of Oxidative Stress In The Protein Damage And Dna Lesion In Alzheimer's Disease Neuropathology, Cheng Zhang

Doctoral Dissertations

Glutathione (GSH) plays an essential role in the intracellular antioxidant defense against the oxidant radicals, especially the ·OH radical. To understand the early and progressive cellular changes in Alzheimer's disease (AD) development, we investigated reduced glutathione/oxidized glutathione (GSH/GSSG) status in a double mutated AD transgenic mouse model (B6.Cg-Tg), which carries Swedish amyloid precursor protein mutation (APPswe) and exon 9 deletion of the PSEN1 gene. Likewise, S-glutathionylation (Pr-SSG) is a specific post-translational modification (PTM) of cysteine residues by the addition of glutathione. S-glutathionylated proteins induced by oxidative stress play an essential role in understanding the pathogenesis of the aging …