Life Sciences Commons^™

Isolation Of Aged Mouse Primary Microglia As A Model System For Alzheimer’S Disease Research, Michael Landis

Biology Honors Papers

Microglia and their role as the immune cells of the central nervous system are an emerging area of interest within Alzheimer’s research, particularly as they have shown in a benevolent and malevolent cellular context. Models of Alzheimer’s disease are very light in studying microglia, so in this study a model of microglia isolated from aged mice is established in order to study the phagocytic activity and protein expression of microglia in response to Amyloid Beta. The cells were isolated from aged mice and cultured before being used to confirm cellular identity, as well as to measure phagocytic activity. This study …

Exploring Available Information On The Gut-Brain Axis And Alzheimer’S Disease For Clinicians Making Dietary Recommendations: A Scoping Review, Megan Gibson

Electronic Theses and Dissertations

Abstract: Alzheimer’s Disease (AD) is a complex neurodegenerative disease that requires interprofessional collaboration. Pharmacological options are currently ineffective, increasing the need for preventative strategies to combat the rise of AD. Considerations of gut-targeted interventions have increased as a key component in the prevention of AD, based on the understanding that the state of the gut microbiome can impact cognitive function through the pathway known as the gut-brain axis.

Methods: This scoping review explored information on the gut-brain axis in persons with AD. A comprehensive search was conducted in November 2023. Forty reviews and 13 human studies were analyzed.

Results: There …

Investigation Of Alzheimer’S Amyloid-Β Protein Aggregation With A New Fluorescent Dye., Emma Alberty

Undergraduate Research Symposium

Alzheimer’s Disease (AD) is the most common form of dementia characterized by the impairment of at least two brain functions such as memory loss and judgement. AD is a progressive illness that can last as many as 20 years. AD is largely considered to be caused by the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. A better understanding of the structure and function of these plaques may lead to clearer understanding of the disease. To analyze amyloid plaques, aggregation assays are often used. During these assays we begin with monomer and place the sample in biological conditions to …

Using A Reverse Visually Guided Reaching Task To Distinguish Between Healthy Aging And Early Alzheimer’S Disease, Brandon Woolman

Dissertations, Master's Theses and Master's Reports

Changes in motor behavior may function as a proxy for cognitive decline. While Alzheimer's disease (AD) is associated with impairments in learning and memory, recent studies suggest that subtle changes in motor task performance may reflect early cognitive changes. For example, the visuomotor rotation task that manipulates visual feedback about hand position during reaching movements, can be used to examine cognitive changes in aging populations. The current study used the reverse visually guided reaching task (rVGR) which rotates visual feedback of participant’s hand position 180⁰ relative to the actual hand position. We sought to expand on previous literature by recruiting …

Utilizing Ai Integrated Neuroimaging Technology To Expand Upon Machine Learning In Positron Emission Tomography Technology With The Aim Of Detecting Amyloid Beta Biomarkers Early In The Onset Of Alzheimer's., Ethan S. Terman

Undergraduate Research Posters

Early intervention in Alzheimer's is vital for treatment. The earlier a professional can detect symptoms and make a diagnosis the earlier a prognosis can be implemented. With the prevalence of data in our day-to-day world combined with Artificial intelligence (AI), utilizing both for machine learning can pave the way for more accurate and efficient detection of Alzheimer's and other neurodegenerative diseases. AI combined with Machine learning (ML) increases diagnostic efficiency and reduces human errors, making it a valuable resource for physicians and clinicians alike. With the increasing amount of data processing and image interpretation required, the ability to use AI …

Characterization Of Pathological Tau Mutants, Charles J. Mcdonald

Dissertations, Theses, and Capstone Projects

Tau is a protein expressed exclusively in glia and neurons in the central nervous system and implicated in several neurogenerative diseases called “tauopathies”. Among all the tauopathies, one third is characterized by the presence of genetic mutations leading to the synthesis of tau proteins with single amino acid substitutions at specific locations and affecting protein function. While most of the initial studies have emphasize the functional role of tau as modulator of the axonal cytoskeleton, it has recently been well accepted that tau is also an intrinsically disordered protein that tends to form membraneless organelles called coacervates, due to a …

Antimicrobial Activity And Mechanism Of Amyloid Proteins And Synthetic Conjugated Polyelectrolytes, Fahimeh Maghsoodi

Nanoscience and Microsystems ETDs

Although the exact cause of Alzheimer’s disease (AD) is still unknown, it is widely considered that the accumulation of amyloid plaques composed of the amyloid-β (Aβ) peptide in the brain is linked to neurodegeneration. Co-localization of viral DNA with Aβ plaques, the association of brain infection and AD, and research indicating the protective effect of Aβ against bacteria and fungi in mice and human cells have led to the hypothesis that Aβ expression and deposition may be central to its function as an antimicrobial peptide (AMP). In my thesis research, we seek to elucidate how Aβ functions as an AMP …

Effects Of Diet On Lcn2 Expression And Onset Of Neuroinflammation In An Alzheimer’S Disease Mice Model, Abdirahman A. Hayir

Neuroscience Honors Projects

This project covers the findings regarding the impact of diet on lipocalin 2 (LCN2) and the effects it has on neuroinflammation Alzheimer’s Disease (AD). LCN2 is a protein that is critical to the functionality of mitochondria and inflammatory responses. Evidence has shown that mitochondrial dysfunction is a potential central event in driving AD pathogenesis and contributing to formation of pathological hallmarks such as chronic inflammation. Furthermore, studies have shown that LCN2 can be deficient under metabolic conditions such as high-fat-diet (HFD). This study investigates if HFD induces LCN2 deficiency and increased neuroinflammation in an AD mice model.

Development Of Graphical Models And Statistical Physics Motivated Approaches To Genomic Investigations, Yashwanth Lagisetty

Dissertations & Theses (Open Access)

Identifying genes involved in disease pathology has been a goal of genomic research since the early days of the field. However, as technology improves and the body of research grows, we are faced with more questions than answers. Among these is the pressing matter of our incomplete understanding of the genetic underpinnings of complex diseases. Many hypotheses offer explanations as to why direct and independent analyses of variants, as done in genome-wide association studies (GWAS), may not fully elucidate disease genetics. These range from pointing out flaws in statistical testing to invoking the complex dynamics of epigenetic processes. In the …

The Relationship Between Circadian Rhythms And Neurodegenerative Disease, Christopher Simpson

Honors Projects

Neurodegenerative disease is a pervasive and insidious disease affecting a large proportion of the elderly population. Leading to the degeneration of neural tissue throughout the nervous system, it is a slow and progressive disorder. Because of its nature, it is possible that it has a connection to circadian rhythms. Circadian rhythms are the endogenous approximately 24-hour rhythms of the body commonly associated with the sleep-wake cycle, but they account for much more. This review aims to ascertain the relationship between the two by covering several facets of research pursued in the past five years. Beginning with establishing a basic understanding …

Alzheimer's Disease: A Comprehensive Review Including Personal Experience From Retirement Home Patients, Sydney Fox

Honors Theses

Alzheimer’s Disease is a neurodegenerative illness and disease, the most common type of dementia, and the sixth leading cause of death (Sá et al., 2012). The disease was discovered in 1906 and named after Dr. Alois Alzheimer, a psychiatrist and neuropathologist. Over time, a variety of hypotheses have developed regarding the cause behind this multifactorial disease, and these will be disclosed in a later section. Nonetheless, the disease was first observed in changes of the brain tissue of a woman who was said to have die from an unusual mental illness with many abnormal bumps. These bumps are now recognized …

A Look Into Alzheimer’S Disease—Interventions At The Molecular Level, Priscila Feliciano Nieves

Honors Undergraduate Theses

There are puzzle pieces to the cure for Alzheimer’s Disease (AD), and such can emerge by inspecting the biomolecular interactions and their effects on neuronal cells. The upcoming presented literature review will cover the molecular changes caused by AD pathological progression, explore the relationship between non-AD molecules and AD molecules in the body, and analyze potential contributing factors in AD. In addition, the information to be provided will highlight medicinal alternatives respective to a particular stage in AD.

Systems Approaches For Gene And Drug Discovery In Alzheimer’S Disease, Jeffrey Brabec

Graduate College Dissertations and Theses

Alzheimer’s Disease (AD) is a devastating neurodegenerative disorder affecting all tissues and cell types of brain leading to emotional dysregulation and cognitive dysfunction. From genome-wide association studies (GWAS), to date we have identified forty-two genome-wide significant genes for AD that influence overall disease risk or endophenotypes, including neuroimaging and gene expression profiles. Nevertheless, the currently known AD genes do not account for a significant proportion of the heritability of disease risk, implying the existence of many weak-effect variants in potentially thousands of genes as drivers of AD outcomes. This genetic architecture, composed of many small effects, is partly due to …

Traumatic Brain Injury-Induced Changes Of Immune/Inflammatory Response In The Context Of Predisposition Of Alzheimer’S Disease, Alexandra Pedin

Theses and Dissertations

Alzheimer’s Disease (AD) is a progressive neurogenerative disease that affects millions globally. At this time there are no effective treatment options as the primary cause for AD is not fully understood. In addition to old age, genetic predisposition, and certain health conditions, traumatic brain injury (TBI) has been identified as a risk factor for AD. While the pathway that links TBI to AD is still largely unknown, the neuroinflammatory response to both conditions has been connected to the NLRP3 inflammasome. Due to its role in the innate immune system and proinflammatory cytokine mediation, the NLRP3 inflammasome could be a potential …

Impact Of Xenobiotics On Neuronal Outcomes, Gabriela Henriquez

Open Access Theses & Dissertations

Neurodegenerative diseases are a common affliction of the Central Nervous System. They are caused by age, genetics, and environmental factors. Alzheimer's disease, Parkinson's disease, Huntington's disease, and Amyotrophic Lateral Sclerosis are well-known among the host of neurodegenerative disorders, with Alzheimer's disease and Parkinson's disease being the leading pathologies across this canvas. It is known that the pathogenesis of neurodegenerative diseases is multifactorial due to the involvement of genetic mutations, radical-induced protein damage, abnormal aggregation of misfolded proteins, and the formation of amyloid deposits. The amyloid proteins in neurodegenerative disease include Tau and Amyloid (Aβ) in Alzheimer's disease and α-Synuclein in …

Characterization Of Biomarkers For Alzheimer’S Disease And Hiv-1 Associated Neurocognitive Disorders, Armando Garces Iii

Theses and Dissertations

Alzheimer’s disease is a neurodegenerative disorder that is characterized by progressive cognitive decline and the accumulation of amyloid beta and neurofibrillary tangles in regions of the brain. These protein deposits are known to generate multiple effects on the brain that lead to neurodegeneration. It has been established that (Human Immunodeficiency Virus) HIV-1 accelerates the aging process of people living with HIV-1. Moreover, there is significant clinical evidence indicating a potential link between the neurodegeneration developed by those with an HIV-1 infection and AD. HIV-1 viral infection causes cognitive impairment known as …

Preventing Alzheimer's: Effects Of Second Language Acquisition In Older Populations, Joshua Rhead

Undergraduate Honors Theses

Alzheimer’s disease continues to be a problem that medicine has few answers for. As a result, much research has been focused on finding a cure as well as interventions to help prevent the onset of the disease. One such intervention that has been proposed is to improve the brain’s efficiency and connectivity. A controversial method of achieving these results is through second language acquisition. Many provide evidence for or against the benefits of this intervention, but much remains unclear. Most of these studies focus on cognitive function and functional connectivity in language areas, but the default mode network, which is …

Determining The Role Of Methylglyoxal (Mgo) And The Trpa1 Channel In Inducing Astrocyte Senescence And Neurodegeneration, Natalie Hill

Natural Sciences and Mathematics | Biological Sciences Master's Theses

Aging is the largest risk factor for the development of Alzheimer’s disease (AD) and related dementias. A recently proposed driver of age-related pathologies is cellular senescence, a phenotype that consists of cell-cycle arrest and an inflammatory response known as the senescence-associated secretory phenotype (SASP). Although there is a link between the accumulation of senescent cells and neurodegeneration, much remains unknown about how senescent cells arise in the brain. Astrocytes are the most abundant cell type in the brain that serve important roles like supporting neurons and proliferating in response to stress. Methylglyoxal (MGO) is a glycolytic byproduct that can react …

Cloning And Functional Characterizations Of Circular Rnas From The Human Mapt Locus, Justin R. Welden

Theses and Dissertations--Molecular and Cellular Biochemistry

Under pathophysiological conditions, the microtubule protein tau (MAPT) forms neurofibrillary tangles that are the hallmark of sporadic Alzheimer’s disease as well as familial frontotemporal dementias linked to chromosome 17 (FTDP-17). In this work, I report that MAPT forms circular RNAs through backsplicing of exon 12 to either exon 10 or exon 7 (12→10; 12→7), and that these circular RNAs are translated into proteins.

Using stable cell lines overexpressing the circular tau RNAs 12→7 and 12→10, we have discovered that the tau circular RNA 12→7 is translated in a rolling circle, giving rise to multiple proteins. This circular RNA …

Bilingualism: A Way To Delay The Onset Of Alzheimer’S Disease And Fight The Global Burden Of Disease It Imposes, Abigail Wester

Regis University Student Publications (comprehensive collection)

Dementia is the second leading cause of death (accounts for 16.5%) and the leading cause of dependency and disability worldwide (GBD 2016 Neurology Collaborators, 2019). This burden associated with dementia falls heavily on family members, communities, and the individuals themselves. When looking at global dementia cases, the numbers are on the rise and expected to triple by 2050 (World Health Organization, 2019; Robinson, Stephan, & Magklara, 2019). The most common type of dementia is Alzheimer’s Disease (AD), which accounts for 60-80% of all dementia cases (DeTure & Dickson, 2019). Characterized by memory impairment and cognitive decline, AD later impacts behavior, …

How The Amino Acid L-Serine Provides Neuroprotection Against L-Bmaa Induced Alzheimer’S Disease, Joseph Cimino

Capstone Showcase

More than 6 million people in America are living with Alzheimer’s Disease (AD) and there are currently no cures or treatments. It is time to move on from the ꞵ-amyloid hypothesis and broaden AD research. New research is suggesting that dietary exposure to a cyanobacterial toxin known as L-BMAA is causing neurodegenerative diseases such as AD, Amyotrophic lateral sclerosis (ALS), and Parkinson’s Disease. L-BMAA is misincorporated during protein folding, in place of the proper amino acid, L-Serine. It has been shown that the naturally occurring amino acid, L-Serine, can provide neuroprotection against L-BMAA, but the mechanism by which L-Serine infers …

Neuroprotection Against Alzheimer’S And Lifespan Extension Induced By Dietary Restriction Are Associated With Metabolomic Changes And Depend On Oxidative Resistance Protein 1 (Oxr1), George W. Brownridge Iii

Natural Sciences and Mathematics | Biological Sciences Master's Theses

Dietary restriction (DR) has been demonstrated to be a robust means of extending the healthspan and lifespan, along with improving cognitive performance in various model organisms from yeast to primates, possibly by mediating neuroprotection. We utilized the Drosophila melanogaster model organism to better understand the molecular pathways that enable DR-induced benefits. By performing a genome-wide associated screening of the Drosophila Genetic Reference Panel (DGRP) that catalogues all natural genetic variants, we discovered that Oxidative resistance protein 1 (OXR1) showed the most significant difference in expression between DR and the inverse intervention of ad libitum (AL). Our research found that OXR1 …

Flavonoid And Cannabidiol Neural Glyoxalase Pathway Enhancement Against Aging And Alzheimer’S Disease, Joel R. Frandsen

Theses & Dissertations

Alzheimer’s Disease is a neurodegenerative condition featuring neural cell death and a decline in cognitive capacity caused by elevated inflammation and production of reactive oxygen species. The glyoxalase pathway is an endogenous antioxidant system that neutralizes reactive methylglyoxal through sequential reactions. Dysfunction of the glyoxalase pathway contributes to oxidative stress and the accumulation of inflammatory metabolic byproducts. Plant-produced compounds with antioxidant activity can enhance endogenous antioxidant pathways and protect cells from elevated ROS production. We hypothesize that flavonoids and limited Cannabis Sativa-produced cannabidiol can enhance glyoxalase pathway function through regulation of antioxidant and pro-apoptotic signaling pathways to prevent methylglyoxal-mediated …

Type Three Diabetes: Are You At Risk? A Systematic Review, Mary Ellen Yep

All Student-Created Educational Resources

To develop a possible framework for informing patients with type two diabetes of their potential risk of dementia, specifically Alzheimer’s Disease. Since type two diabetes is still on the rise, this could implicate a major increase in dementia across the population. Implications to assess the public of this research to promote awareness of the risks of type 3 diabetes.

The Association Of Late-Life Depression, Cognitive Functioning, And Sleep Disorder In Aging, Jessica B. Aronis

Electronic Theses and Dissertations

The continuing growth in the demographic of aging individuals in the United States creates concern for diseases of aging that are chronic, notably unipolar depressive disorders. The high rates of depression in the aging population are a concern because of the strong association between late-life depression and cognitive impairment. Poor cognitive functioning is a hallmark of aging related neurological disorders, the most prevalent being Alzheimer’s Disease (AD). Sleep disorder is a core symptom of depression, and is definitively associated with the development of mild cognitive impairment (MCI), the prodrome of AD. MCI is also characterized by similar types of sleep …

Analysis Of The Gut-Brain Axis In Aging: Implications In Alzheimer Disease, Molly Martin, Mary Austin, Denah Appelt

Research Day

The gut microbiome is comprised of the shared genome of the trillions of microorganisms residing in the gastrointestinal ecosystem. The interaction between the host and its gut microbiome, the Gut-Bran Axis (GBA), is a complex relationship whose management could prove critical to preventing or treating not only various gut disorders, like irritable bowel syndrome (IBS) or behavioral health disorders such as general depression and anxiety, but also central nervous system (CNS) disorders, such as Alzheimer's (AD) and Parkinson's (PD) diseases. The purpose of this review is to summarize what is currently known about the gut microbiome, how it is connected …

Design And Synthesis Of A Novel Lsoxazoline As A Potential Pam-Agonist, Josselyn Roosenberg

Honors Theses

Progression of Alzheimer's disease is associated with a loss of Ml receptor activation in the brain. However, a lack of clinical success following attempts to activate the Ml receptor at the orthosteric site has contributed to a transition towards the allosteric pocket of the receptor. Here, positive allosteric modulators (PAMs) interact to potentiate the acetylcholine response. Recent research proposes that optimization of PAM activity at the expense of intrinsic agonism may posit a means to limit adverse side effects. Therefore, this project proposes a design and synthesis of a novel isoxazoline as a potent PAM agent with weak intrinsic agonism.

The Master Synaptic Regulator: Activity Regulated Cytoskeleton Associated Protein, Arc, In Normal Aging And Diseases With Cognitive Impairment, Amber Khan

Dissertations, Theses, and Capstone Projects

Alzheimer’s disease (AD) is a progressive neurodegenerative disease with complex underlying pathogenic mechanisms. Epidemiological studies have forecasted that in the next 3 decades, the number of AD cases will rise to epidemic proportions with enormous medical, emotional and financial burdens impacting individuals affected and society. Among many risk factors for AD, advancing age is clearly essential and necessary. Revelation of molecular changes in synaptic activities leading to the prodromal, mild cognitive impairment (MCI) stage may help illuminate the course of pathogenic progression and its cause-effect relationship with various targets thereby enabling target-driven disease-modifying therapeutic agents for AD.

Activity-regulated cytoskeleton-associated (Arc) …

Mechanisms Of Microglia Mediated Apolipoprotien E Neurotoxicity, Pardeep Singh

Dissertations and Theses

No abstract provided.

Regional Specialization Of The Adult Meninges Supports Different Brain Areas And Alters With Age, Christina Ann Calabrese

Legacy Theses & Dissertations (2009 - 2024)

The meninges comprise three heterogeneous connective tissue coverings, referred to as the dura, arachnoid, and pia mater, which completely envelop the brain and spinal cord. Given the meninges’ vast coverage over the entire CNS and its unique development, I hypothesized that regional leptomeninges (arachnoid and pia mater layers combined) provide specialized support to different brain areas. During development, anterior meninges, overlying the frontal cortex, derive from neural crest cells that are ectodermal in origin. Posterior meninges, overlying the midbrain to the spinal cord, derive from a mesodermal lineage. This difference in lineage and location suggests potential functional differences between the …