Nervous System Diseases Commons^™

Mapping The Neuroexposome: Integrative Analysis Of Dementia Risk Factors Through Multi-Omics And Environmental Profiling In The Egyptian Population., Mai Ahmed Saadzaghloul Othman

Theses and Dissertations

Background: Dementia represents one of the most pressing public health challenges of the twenty-first century, with the global burden projected to reach 153 million cases by 2050. Egypt, as the most populous Arab nation, faces a corresponding rise in age-related diseases, yet comprehensive data from low- and middle-income countries remain severely limited. The neuroexposome framework, integrating genetic susceptibility, environmental exposures, and metabolic alterations, offers a powerful strategy to characterize the complex interplay between internal and external risk factors for Alzheimer's disease (AD) and Alzheimer's disease Related Dementias (ADRD).

Objectives: This thesis aimed to: (1) examine the distribution of APOE alleles …

Mechanisms Mediating The Protective Effects Of Caffeine On Alzheimer’S Disease Progression, Jessica Ivanov, Malky Bernat, Joshua Drawbaugh, Jeremy Mehta, Namira Rahmani, Saikumar Thellapally

Rowan-Virtua Research Day

Background: This review aims to examine the molecular mechanisms through which caffeine may exert neuroprotective effects against Alzheimer’s Disease (AD).

Methods: A literature review was done across PubMed and Embase to identify studies between 2000 and 2024, exploring the mechanism behind caffeine’s effects on AD. The criteria focused on peer-reviewed articles involving human or animal models. Information was gathered on study design, participant characteristics, caffeine consumption, proposed mechanisms, and effects on cognition.

Results: The studies support caffeine's potential as a therapeutic, neuromodulator against AD through six mechanisms: inhibition of adenosine A2A receptors, decreased amyloid-beta production and aggregation, promotion of amyloid …

Antibody Therapies For Alzheimer's Disease, Alexandra Zerr

University Honors Theses

Alzheimer's Disease (AD) is the leading cause of dementia worldwide. Patients with this condition first experience mild cognitive impairment, followed by the loss of memory, cognitive skills, identity, and the ability to perform daily tasks unassisted, eventually culminating in death.

The dominant hypothesis for the mechanism of Alzheimer's, the amyloid cascade hypothesis, based on early-onset AD, suggests that amyloid plaques formed by Aβ peptides cause a cascading effect involving an increase in toxic tau protein, which is correlated with the disease progression of Alzheimer's patients. While the mechanism of late sporadic AD is not fully understood, this has been used …

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 …

Alzheimer’S Disease Studies In The Tex-Mex Border: Dissecting A Complex Multifactorial Problem, Ney Alliey-Rodriguez, Rosa V. Pirela, Alvaro Diaz-Badillo, Karla Lopez Lorenzo, Noe Garza, Frank Gilliam, Eron G. Manusov, Gladys E. Maestre

Research Symposium

Purpose: Alzheimer’s Disease (ALZ) is the leading cause of dementia in the aging population, and Latinos have >3 times higher risk to develop dementia than the overall US population. Although several studies have examined for possible causes of this increased risk, lack of comprehensive information plus a reduced number of Latino samples available in each study have hindered the answers.

Description: The University of Texas Rio Grande Valley has joined two large studies looking for multiple biomarkers associated with ALZ: The South Texas Alzheimer’s Center Clinical Data Repository and Biobank (STAC) and the Texas Alzheimer’s Research and Care Consortium (TARCC). …

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.

Infiltrating Cd8+ T Cells Exacerbate Alzheimer’S Disease Pathology In A 3d Human Neuroimmune Axis Model, Jefin Jose, Devam Purohit

VCU's Medical Journal Club: The Work of Future Health Professionals

In this study, Jorfi et al. employed a neuroimmune axis model containing neurons, astrocytes, and microglia to examine the role of immune cells in Alzheimer's disease. Jorfi et al. found that T cells selectively infiltrated the BRAIN compartment of the neuroimmune axis model as compared to B cells and monocytes. Jorfi et al. further found that CD8+ T cells demonstrated heightened cytotoxicity in the Alzheimer's disease brain, illuminating the role of immune cells in neurodegeneration. Upon further examination, the CXCR3-CXCL10 signaling pathway was found to have an important role in inflammation.

Exploring Risk Factors Of Alzheimer’S Disease Using Mouse Models, Xian Han

Theses and Dissertations (ETD)

Mouse models of Alzheimer’s disease (AD) that accurately recapitulate pathology and molecular changes are crucial for understanding disease mechanisms and subsequent therapeutic development. We examined five commonly used mouse models of AD (5xFAD, J20, APPNL-F, APPNL-G-F, Tau P301S) and compared their whole- and phosphoproteomes with human AD (the integration of three published datasets) to study whether they can mimic protein/RNA expression discrepancies, molecular changes, and enriched pathways found in human AD cases. The mouse models especially 5xFAD and APPNL-G-F show proteomic signatures similar to human AD but lack human-specific AD progressions, such as dysregulation of synaptic pathways and networks. Integration …

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

Dissertations and 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 …

Immunomodulatory Roles Of The Lysosomal Sialidase Neuraminidase 1, Leigh Ellen Fremuth

Theses and Dissertations (ETD)

Background Sialic acids are key sugar moieties located at the non-reducing terminals of glycan chains on glycoproteins and glycolipids. By virtue of their location, they influence the functions and biochemical properties of the macromolecules they are bound to. Removal of sialic acids in mammalian cells is carried out by four sialidases, which are differentially expressed and localized in distinct subcellular compartments. Neuraminidase 1 (NEU1), the most abundant and ubiquitous of the four sialidases, functions primarily in the acidic environment of the lysosomes, but can hydrolyze substrates at the plasma membrane, at least in certain cell types. The enzyme initiates the …

Enhancing Engagement In Older Adults With Alzheimer's Disease At A Reminiscencce Therapy Adult Day Center, Kendra C. Gillio

Student Capstone Papers

Alzheimer’s disease is a degenerative form of dementia, which can impair an individual’s executive functioning, orientation, and memory; ultimately leading to mood and behavior changes (Alzate, 2018). Alzheimer’s disease is the most common form of dementia, affecting approximately 60% to 70% of the older adult population aged 65 and older (Santos da Silva, de Oliveira Alves, Barros Leite Slagueiro & Bezerra Barbosa, 2018). Currently, the number of individuals with dementia is estimated at approximately 50 million people worldwide and is expected to climb to 152 million people by the year 2050 (Rathbone, et. al, 2019). Damage to the brain develops …

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) …

Protein Aggregates And Polyglutamine Tracts In Neurodegenerative Disease, John Mack

Senior Honors Theses

The incidence of neurodegenerative diseases such as Alzheimer's Disease, Parkinson's Disease, Huntington's Disease and other Polyglutamine Diseases is projected to dramatically increase throughout the developed world, and yet the pathology of these diseases remains poorly understood. One pathway that these neurodegenerative diseases share is the accumulation of pathologic proteins which are not only harmful in their soluble form but may go on to form toxic aggregates. In many cases, a consensus has yet to be reached concerning the mechanism for protein aggregation. Therefore, the exploration of the roles of these proteins and their possible mechanisms, along with potential techniques for …

Ethical Dilemma Of Alzheimer's Disease And Informed Consent, Daenia La Rodé

Augustana Center for the Study of Ethics Essay Contest

No abstract provided.

An Isogenic Stem Cell Model Of Alzheimer's Disease: Direct Expression Of Amyloid-Beta, Teresa Marie Ubina

Electronic Theses, Projects, and Dissertations

Alzheimer’s disease (AD), identified over 100 years ago and intensively studied since the 1970s, has no effective treatments or mechanistic understanding of the underlying neurodegenerative process. Most investigators believe accumulation or aggregation of amyloid beta (Ab) proteins plays a causative role. Aβ peptides (~39-43 residues) are generated by proteolysis of the transmembrane protein APP. One reason we know so little about AD is an incomplete understanding of the cellular mechanisms responsible for Ab proteotoxicity. Human ES and iPSC models of AD are recent additions to many other models used to investigate these mechanisms. AD, however is a chronic progressive condition …

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 …

Gene Expression Profiling In An Alzheimer's Disease Mouse Model, Matthew R. Dalton

Senior Honors Theses

Explaining precisely how Alzheimer’s disease (AD)—the world’s most common form of dementia—materializes in the human brain has proven to be one of the most elusive ends in modern medicine. Progressive memory loss, neurodegeneration, and the presence of abnormal protein aggregates of amyloid-beta (Aβ) and neurofibrillary tangles (NFT) characterize this disease. Genome sequencing provides researchers with the ability to better identify disease-related changes in gene expression, some of which may play a role in the initiation and progression toward the AD-like state. Intimate interactions between tissues have been observed in many diseases, particularly between the brain and blood. This analysis seeks …

Analysis Of Differential Mrna And Mirna Expression In An Alzheimer’S Disease Mouse Model, Amanda Hazy, Matthew Dalton

Other Undergraduate Scholarship

Research has shown that changes in gene expression play a critical role in the development of Alzheimer’s Disease (AD). Our project will evaluate genome-wide RNA expression patterns from brain and blood in an AD mouse model. This analysis will provide insight regarding the mechanisms of AD pathology as well as determine a possible diagnostic tool utilizing RNA expression patterns found in the blood as biomarkers for AD.

Epigenetic Remodeling In An Imr-32 Cell Line And Transgenic Mouse Model Of Alzheimer's Disease, Matthew S. Baker

Senior Honors Theses

The pathological features of Alzheimer’s disease (AD) have been researched and documented extensively, however the causes of these features are still unknown. The following studies sought to determine if epigenetic methylation alterations contribute to AD. Two studies were sequentially carried out, first using an IMR-32 model and then using a transgenic mouse model overexpressing beta-amyloid. A few assay and confirmation methods were carried out to determine the promoter regions in disease state models undergoing drastic change, and the genes linked to these promoter regions were analyzed to determine significant gene ontology being altered by this epigenetic modification. This data was …

Analysis Of Autophagy And Inflammasome Regulation In Neuronal Cells And Monocytes Infected With Chlamydia Pneumoniae: Implications For Alzheimer’S Disease, Brian J. Balin, Christine J. Hammond, Juliana Zoga, Ahmad B. Cader, Annette K. Slutter, Jonathan M. Anzman, Ian Kohler, Susan T. Hingley, Denah M. Appelt

Scholarly Posters

Objectives: Our laboratory has been studying the role of infection with the obligate intracellular bacterium Chlamydia pneumoniae in sporadic late-onset Alzheimer disease (LOAD). This infection may be a trigger for the pathology observed in LOAD as a function of initiating changes in gene regulation following entry of the organism into the brain. As such, we are analyzing how this infection can promote changes in autophagy and inflammasome gene regulation as both have been shown to be altered in LOAD. Methods: Human SKNMC neuronal cells and THP1 monocytes were infected in vitro for 24-72 hrs with a laboratory strain of Chlamydia …

Binding Efficacy Of Different Polyphenolic Phytochemicals With Β-Lactoglobulin And Human Serum Albumin: Implication For Therapeutics Against Neurodegenerative Diseases, Rene Duran^, Andres Ortiz^, Mahesh Narayan*, Vladik Kreinovich*

COURI Symposium Abstracts, Spring 2012

No abstract provided.

Investigating The Impact Of Cd147 And Its Expression On Neurodegenaration And Alzheimer's Disease (Ad), Limbikani J. Kanyenda

Theses: Doctorates and Masters

CD147, also known as basigin, extracellular matrix metalloproteinase inducer, neurothelin, tumour cell-derived collagenase stimulatory factor, M6, HT7, OX47 or gp42, is a transmembrane glycoprotein of the immunoglobulin super-family. It is expressed in many neuronal and non-neuronal tissues with high expression in the hippocampus, pre-frontal cortex, thyroid, heart, early erythroid, amygdala and placenta. This protein is involved in various cellular and biological functions such as lymphocyte migration and maturation, tissue repair, cancer progression, T and B lymphocyte activation and induction of extracellular matrix metalloproteinase. The CD147 protein interacts with with cyclophilin A, cyclophilin B, sterol carrier protein, caveolin-1 and integrins, and …

Characterization Of Amino Acid Residues Integral To Neuronal Binding Of Amyloid Beta Protein In Alzheimer’S Disease, Nicole C. Olson

Chemistry and Biochemistry

Purpose:  Alzheimer’s Disease is a neurodegenerative disease resulting from over-production and neuronal accumulation of amyloid-beta proteins (Aβ40/Aβ42). The glycine residue at position 33 and histidine residues at positions 13 and 14 are involved with binding and internalization of these proteins, actions potentially inhibited by substituting or sterically hindering these residues with an antibody specific to positions 2-11 (IgG-4.1). Rat pheochromocytoma (PC12) cells differentiated with nerve growth factor were used as a neuronal model to determine whether substitution and/or antibody block amyloid-beta’s neuronal interactions.

Methods:  PC12 cells were incubated with fluorescein-labeled-amyloid-beta-40 (F-Aβ40) or substituted F-Aβ40 derivatives (F-Aβ40-H13,14G, F-Aβ40-H13,14G;G33A), with or without …

Finding The Pill On The Floor: How Contrast Sensitivity Affects Daily Living Skills In Alzheimer’S Disease Patients, Marlyn Colon

Undergraduate Review

Alzheimer’s disease (AD) is a progressive brain disorder that gradually destroys an individual’s mental functioning and social capabilities, including the ability to carry out everyday activities. Although memory deficits affect AD patients’ ability to perform these activities, research suggests that visual perception impairments also contribute. One impaired visual perception ability, contrast sensitivity, enables one to distinguish an object from its immediate surroundings. The present project measured contrast sensitivity in a real-world task by having AD patients find a pill of various shades of gray on a tiled background. Results were compared to young and elderly control participants. Participants also filled …

Alzheimer's Disease And Contrast Sensitivity: Implications For Everyday Functioning, Sandra Neargarder

Bridgewater Review

No abstract provided.