Digital Commons Network^™

From Tradition To Transition: Evaluating Culinary Medicine As A Tool For Metabolic Health Among Nigerian Immigrants In The United States And The United Kingdom, Simi Oduwole M.S.

Department of Nutrition Student Projects

This scoping review examines existing publications to evaluate whether Culinary Medicine can be used as a tool for metabolic health among Nigerian immigrants in the United States and the United Kingdom. Nigeria is one of the fastest-growing populations globally, with increasing migration to high-income countries such as the United States and the United Kingdom. Evidence suggests that Nigerian immigrants experience a rise in diet-related chronic diseases, including obesity, diabetes, and cardiovascular disease, as duration of residence increases. This phenomenon is often attributed to dietary acculturation and shifts toward Westernized eating patterns. This scoping review evaluates whether culinary medicine can mitigate …

Sex Differences In Proteomic Response To Ischemic Stroke, Christopher J. Mclouth, Hunter S. Hazelwood, Jacqueline A. Frank, Jordan P. Harp, David Dornbos, Justin F. Fraser, Keith R. Pennypacker

University Faculty Publications and Creative Works

Background: Women often experience greater disability after ischemic stroke than men, but the biological mechanisms underlying these differences remain unclear. Proteomic analysis may identify sex-specific molecular pathways that contribute to stroke rehabilitation and recovery.

Methods: We analyzed plasma samples from 141 patients enrolled in the Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC). Expression of 184 inflammatory and cardiometabolic proteins, measured proximal and distal to the clot, was quantified using Olink panels. Associations between protein expression and discharge outcomes – including the National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS), and Montreal Cognitive Assessment (MoCA) – …

Development Of Resources To Support Independence In And Access To Nature-Based Activities, Riley Carpender

Capstone Projects

This capstone paper discusses the need for resources that support independence in and access to nature-based activities that support health and wellbeing. Occupational therapists (OTs) have expertise in recommending and implementing adaptations to increase individuals’ engagement in nature-based activities. There is currently a gap in the literature regarding access to nature-based activities, and a lack of understanding of how these activities may be implemented, either by caregivers, educators or healthcare professionals. During my capstone I created a guide with modifications for gardening activities for children, wrote an article on how to adapt nature journaling to be more accessible, coded and …

Organic Synthesis Of A Hydrazine Functionalized Ammonium Compound For Improved Capture Of Aldehyde Metabolites From Exhaled Breath, Po'iu N. Burgo

Undergraduate Theses

Breath analysis has emerged as a non-invasive and inexpensive way to screen for respiratory diseases. This technique involves measuring concentrations of specific metabolites found in exhaled breath that serve as a biomarkers for disease. A subclass of volatile organic compounds called α,β-Unsaturated aldehydes, products of the lipid peroxidation mechanism, are underrepresented as biomarkers of lung cancer. These have been found to have relatively increased concentrations in the exhaled breath of lung cancer patients compared to a healthy patient. One of the reasons that these metabolites have been underreported is that the techniques used to measure and characterized exhaled metabolites do …

Maternal Inflammation Alters Nuclear And Mitochondrial Dna Methylation Patterns In Neonatal Brain Monocytes, Andrew Ebenezer, Jonathan Hicks, Brooke Hollander, Alexander Hone, Mona Batish, Robert Akins, Adam Marsh, Elizabeth Wright-Jin

Department of Medicine Faculty Papers

Neonatal hypoxic ischemic encephalopathy (HIE) is a common birth complication that can cause death or lifelong disabling conditions like cerebral palsy, epilepsy, and autism. It is well established that maternal infection and inflammation are significant risk factors for HIE but reasons for this increase in neurological risk to the offspring remain unknown. Inflammation or infection are associated with epigenetic changes and may contribute to the increased risk of neurodevelopmental disability in exposed offspring. Here, we analyzed and compared DNA methylation patterns in brain monocytes isolated from control, maternal immune activation (MIA), and an inflammation sensitized HIE (IS-HIE) CF-1 mouse model …

A Rare Presentation Of Extra-Appendiceal Mucinous Neoplasm Of The Anus, Pincus Joshua, Marianne Estrada, Lance Horner University Of Nevada, Las Vegas

School of Medicine Research Poster Showcase

Introduction: Mucinous neoplasm of the anus is an uncommon malignancy, representing less than 3% of all anal cancers. Even more rare is extra-appendiceal mucinous neoplasm. As a result, limited literature exists to define diagnostic strategies and optimal management. Our case report details the presentation and management of a patient with recurrent mucinous neoplasm of the anus. Methods: A retrospective chart review was performed which includes clinic documentation., operative notes, pathology reports. Results: The patient is a 76-year-old male with a history of T3N0M0 anal mucinous carcinoma diagnosed in 2015 and treated with neoadjuvant chemoradiation with complete pathological response. In 2024, …

Starting With Story, Not Symptom: Narrative Collapse And Cultural Repair In Appalachia, Wayne Coombs Ph.D.

Journal of Appalachian Health

Appalachia’s opioid crisis reflects uneven burdens, especially in distressed coalfield counties, and it cannot be solved by symptom tracking alone. This commentary argues for a narrative shift, starting with story and cultural repair alongside clinical care. Narrative collapse is defined here as the loss of shared, dependable public meaning across groups, not the absence of storytelling in families, churches, and recovery circles. Trauma science suggests that chronic threat reshapes nervous systems across generations, making safety a prerequisite for renewed trust. Drawing on narrative identity research, the piece proposes peer story work as infrastructure that can reduce shame, support treatment engagement, …

Alzheimer’S Is A Delivery Problem: A Neurosurgery-Enabled Evidence Map Of Focused Ultrasound Blood-Brain Barrier Opening As A Cns Delivery Platform, Gargee Sree Nallanukala, Veer Nallanukala, Lauren Noto-Bell, Jacquelyn Gerhart

Research Day

Introduction: Disease-modifying therapies for Alzheimer’s disease (AD) provide modest benefit in selected early-AD populations, but their use is limited by safety risks (e.g., amyloid-related imaging abnormalities [ARIA]) and intensive monitoring. A key reason many therapies underperform is that the blood–brain barrier (BBB) acts like a protective “filter,” allowing only a small fraction of systemically delivered drugs, especially large molecules, to reach the brain. MRI-guided focused ultrasound, paired with intravenously administered microbubbles, can temporarily and locally “loosen” the BBB at a chosen brain region, then allow it to reseal. This approach is being studied as a noninvasive delivery platform that could …

Cardioprotective Role Of Spermidine In Ischemia-Reperfusion Injury, Isabella Brosious, Robert J. Barsotti, Lindon H. Young, Qian Chen

Research Day

Introduction: Timely reperfusion of the heart to restore blood flow and oxygen is critical to rescue ischemic myocardium in the setting of myocardial infarction and reduce cardiac morbidity and mortality. However, reperfusion following prolonged ischemic injury exhibits salvaging, but paradoxically, additional cellular damage, contributing to a larger infarct size. Termed ischemia-reperfusion injury (IRI), the myocardium undergoes various pathophysiological changes following reperfusion – such as apoptosis, oxidative stress, and mitochondrial dysfunction – thus exacerbating cellular damage and death caused by ischemic injury. The research on attenuation of IRI is critical to maximize the benefit of reperfusion. Spermidine is a natural polyamine …

Significant Response To Third-Line Zenocutuzumab In Metastatic Nrg1 Fusion–Positive Pancreatic Adenocarcinoma: A Case Study, Sarah Davis, Sukhrob Makhkamov, Vladimir Limonnik

Research Day

Background

Pancreatic adenocarcinoma is an aggressive malignancy with limited treatment options. In metastatic disease, first‑line regimens like FOLFIRINOX or gemcitabine plus nab‑paclitaxel provide modest survival benefits and are commonly limited by toxicity and disease progression.

Recent advances in precision oncology have identified genomic alterations in a subset of pancreatic cancers. Neuregulin‑1 (NRG1) gene fusions occur in < 1% of pancreatic adenocarcinomas and lead to activation of HER3 signaling through interaction with HER2, promoting tumor growth and survival.

Zenocutuzumab is a bispecific monoclonal antibody designed to target HER2 and HER3. By binding HER2 and preventing ligand-induced activation of HER3, zenocutuzumab disrupts NRG1-driven signaling while preserving HER2 receptor engagement for antibody-mediated targeting. In the eNRGy trial, zenocutuzumab achieved an objective response rate of …

Osteoporosis Is A Risk Factor For Complications And Reoperations At 1 And 3-Years After Arthroscopic Rotator Cuff Repair, Cameron M. Brown, Andrea H. Johnson, Jane C. Brennan, Matthew A. Peterman, Daniel E. Redziniak, Justin Turcotte

Research Day

Introduction

Osteoporosis is associated with compromised bone quality and healing potential. Arthroscopic rotator cuff repair (RCR) restores shoulder function and reduces pain in patients with rotator cuff pathology. The influence of osteoporosis on complications and long-term outcomes following RCR remains underexplored. This study aims to evaluate the relationship between osteoporosis and outcomes after arthroscopic RCR.

Methods

The PearlDiver Mariner 170 dataset was retrospectively analyzed. Patients were grouped by whether they had a diagnosis of osteoporosis within the year prior to RCR. The two groups were propensity score matched 1:1 on age, gender, and comorbidities. Outcomes were assessed at 1-year and …

Evaluating Motivation In Stem Education: A Positive Self-Talk Intervention, Tiffany Copeland, Richard Allen, Sophia Pham, Kristin Gagnier

Research Day

INTRODUCTION: This study evaluated a social-emotional learning intervention that taught positive self-talk to high school students from underrepresented minority groups in science, technology, engineering, and math (STEM). The setting of this study was a place-based program that immersed students in hands-on STEM activities while located in Philadelphia’s life science hub. Before taking a science assessment, students set effort-based goals and learned to say self-talk statements such as “I will give my best effort” and “Even when it's hard, I will give 100%.”

METHODS: This mixed-methods program evaluation compared pre- and post-intervention data using a paired-samples t-test, linear regression, and correlation …

A Case Of Extensive Suprasellar Meningioma Presenting With Insidious Visual Impairment, Vincent Bulzoni, Benedict Uzorka, Peter Maduka Jr

Research Day

Introduction: Meningiomas are generally benign CNS tumors with a propensity to occur in individuals with predisposing risk factors, such as, neurofibromatosis type II. These tumors can arise via de novo mutations, or through inheritance via NF2, and SMARCB1 mutations. They can also arise idiopathically. In this case, A 33-year-old female presented to the ophthalmology clinic for a routine diabetic fundus exam. She also complained of worsening left eye (OS) vision, which had historically been her weaker eye. She had been a type II diabetic for 2.5 years with a most recent HbA1c of 13.6. The patient reported poor OS vision …

Neutralization Of Interferon-Beta Promotes Hivspecific Car T Cell Engraftment And Proliferation, Tyler H. Yang, Sophia Mohammed, Matt Fair, Colby Maldini, Zhe Yuan, Luis Montaner, Daniel Claiborne

Research Day

Introduction: Even in antiretroviral therapy-treated people with HIV (PWH) exhibiting controlled viremia, infection is characterized by a sustained activation of type I interferon (IFN) pathways. Indeed, IFNβ is persistently expressed in the tissues of PWH, and the anti-proliferative effect of IFNβ represents an unappreciated hurdle to immunotherapies aimed at achieving an HIV functional cure.

Objectives: The primary objectives are to i) characterize the anti-proliferative effects of IFNβ on HIV-specific CAR T cells, ii) describe the mechanism(s) underlying IFNβ-mediated attenuation of CAR T cell function, and iii) devise base-editing strategies to ameliorate the negative effects of IFNβ on HIV-specific CAR T …

The Effects Of Bone Health And Variation On Saw Mark Signatures, Lily A. Ambrose, Richard A. Gonzalez

Research Day

Introduction

Bone health and structural variation are multifactorial. Population, environment, age, diet, and health influence the overall functional morphology of bone and its response to stressors. Reduced cortical porosity, trabecular thinning, and low bone mass are common indicators of age-related and pathological changes, affecting a significant portion of the population. Because of this, bones encountered in medicolegal investigations often differ from what is considered “normal.” The structural integrity of bone needs to be considered because density influences mechanical strength and response to external forces.

In criminal dismemberment cases, forensic scientists analyze saw marks to identify tool class and reconstruct events. …

Vaginal Rectopexy For Rectal Prolapse In Advanced Pelvic Organ Prolapse: A Review Of Surgical Strategies, Williams Cheau, Ebony Isagba, Mykala Jackson, Sabirah Smith, Alexandria Neal

Research Day

Pelvic organ prolapse (POP) is a common condition in women, frequently involving the anterior or posterior vaginal compartments. While biologic grafts are increasingly used in cystocele repair, their application in rectocele repair remains rare and underreported.

A 61-year-old female presented with fecal incontinence, mixed urinary incontinence, and symptomatic pelvic organ prolapse, including a stage II midline cystocele, rectocele, and suspected rectal prolapse. She was scheduled for anterior and posterior vaginal wall repair.

This case illustrates a novel use of biologic grafting in rectocele repair with concurrent rectal prolapse management. While graft use in anterior repairs is becoming more common, its …

Severe Postpartum Hypertension And Acute Heart Failure Exacerbation In A 34-Year-Old African American Woman: Implications For Maternal Mortality And Racial Disparities, R. Neha Vangimalla, Allison J. Tresner, Christine A. Lurie

Research Day

Introduction: Postpartum hypertension and cardiomyopathy remain significant contributors to maternal morbidity and mortality in the United States, disproportionately affecting African American women. We present the case of a 34-year-old African American G6P3124 with a history of chronic hypertension and suspected peripartum cardiomyopathy. The patient presented four days postpartum with acute shortness of breath and orthopnea. Pregnancy was complicated by poorly controlled underlying chronic hypertension with worsening dyspnea requiring induction of labor at 36 weeks gestational age (GA) and prior hospitalization for volume overload, dyspnea, and COVID-19 at 33 weeks GA.

Case Description: On presentation, the patient was found to have …

Socioeconomic Determinants Of Hypertension And Complications In Georgia: Age-Stratified Analysis Of The All Of Us Cohort, Daniel Chanelo, Marisela Benitez, Thomas Last

Research Day

Introduction: Hypertension (HTN) contributes disproportionately to cardiovascular morbidity and mortality in Georgia. While demographic disparities in prevalence are well characterized, less is understood about how socioeconomic conditions shape both hypertension risk and downstream complication burden. We examined two questions: Question A - what factors are associated with hypertension presence compared to controls, and Question B - among hypertensive patients, what factors predict complications, with particular interest in whether associations varied by age stratum.

Methods: Retrospective cohort study using the All of Us Controlled Tier dataset. Hypertension required ≥2 diagnostic codes. Participants were restricted to Georgia ZIP3 prefixes (300–319, 398), yielding …

Abdominal Aortic Aneurysm As A Marker Of Systemic Atherosclerosis In A Patient With Prior Coronary Bypass And Fatal Middle Cerebral Artery Stroke: A Cadaveric Case Study, Jordan B. Ahlgren, Azmeer Imran, Rachel K. Ransom, Akosua A. Crumbsy, Lindsey D. Cohen, Angela V. Covington, Mphatso J. Onyekachi, Shiv Dhiman

Research Day

INTRODUCTION: Abdominal aortic aneurysm (AAA) is frequently associated with systemic atherosclerotic disease and increased risk for cardiovascular morbidity. The development of AAA is attributed to hypertension, smoking tobacco, and other factors such as genetics. Patients with vascular diseases also develop multisystem involvement, including coronary, cerebrovascular, and cardiac conduction abnormalities. The purpose of this case study was to investigate the role artherosclerotic disease played the in the fatal left middle cerebral artery (MCA) ischemic stroke of a 75-year-old male with a visible abdominal aortic aneurysm, history of coronary artery bypass grafting (CABG), and permanent pacemaker implantation.

METHODS: Systematic gross anatomical dissection …

Case Report Highlights Disproportionate Health Outcomes Of Rheumatoid Arthritis In Patients Of Lower Socioeconomic Status, Victoria Pfennig, Karen Vega

Research Day

Introduction

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that affects the synovial lining of joints and may lead to progressive joint destruction, disability, and premature mortality if inadequately treated. Increasing evidence demonstrates that social determinants of health, particularly socioeconomic status (SES), significantly influence disease outcomes in patients with RA. Studies have shown that individuals of lower SES experience higher disease activity scores, greater physical disability, and poorer quality of life compared with patients of higher SES. Additionally, lower SES has been associated with longer delays between diagnosis and initiation of disease-modifying antirheumatic drugs (DMARDs), contributing to disease progression …

Targeting Dysbiosis: Rebyota As A Novel Strategy For Recurrent Cdi Prevention, Christina Cologer, Mishel Alvarez, Sia Christine, Brooklyn Myers, Kaytlin Pal, Katrina Strand, Vicky Mody, Shashidharamurthy Taval

Research Day

Clostridioides difficile is a bacterium that colonizes a patient's gastrointestinal tract after the use of systemic antibiotics. This infection, also called CDI, causes severe diarrhea and can be life-threatening. In some patients, CDI recurs, creating a dangerous cycle. Recurrent CDI (rCDI) persists because systemic antibiotics induce dysbiosis, disrupting the gut microbiota’s metabolic functions and compromising the intestinal epithelial barrier. This study was conducted as a literature review evaluating the safety, efficacy, mechanism of action, and clinical use of Rebyota in preventing rCDI. Rebyota is the first FDA-approved (2023) live biotherapeutic designed to restore eubiosis in adult patients after antibiotic treatment. …

Histologic Heterogeneity In Bladder Neoplasia: Identification Of Coexisting Urothelial Dysplasia, Papillary Lesions Of Low Malignant Potential, And Muscle-Invasive Urothelial Carcinoma, Maxwell Trettin, Yousra Abo-Elhamd, Aidan Huckestein, Byron Her, Xiunely Ricano Cadenas, Shiv Dhiman, Rasheed Agboola, Neveen Said

Research Day

BACKGROUND: Urothelial bladder carcinoma (UBC) accounts for approximately 90% of bladder cancers with a male to female prevalence of 3:1. Established risk factors include exposure to tobacco smoking, and environmental and occupational exposure to polycyclic aromatic hydrocarbons and aromatic amines. Additional risk factors include air pollution, advanced age, and occupational exposure to carcinogens present in dyes, paints, petroleum products, and metals. UBC are recognized for their heterogeneous characteristics due to urothelial epithelium exhibiting diverse transcriptional and mutational profiles that evolve within the tumor microenvironment. Additionally, bladder cancers are often found to be multifocal, highlighting the importance of thorough examination of …

Feasibility Of Transcranial Magnetic Stimulation For Treatment-Resistant Depression In Rural Healthcare Settings: A Case Series, Posey Kent, Brandon Krout, Kennedy Johnson, Jodeci Mitchell, Hania Hashmi, Blessing Adeyemo, Ashlee Cook

Research Day

Introduction

Major depressive disorder (MDD) is one of the most common mental health disorders world- wide, with up to one-third of patients experiencing treatment-resistant depression despite adequate pharmacologic therapy. Transcranial Magnetic Stimulation (TMS) is an FDA-approved, noninvasive treatment shown to improve depressive symptoms in treatment-resistant depression. However, access to advanced psychiatric interventions remains limited in rural communities due to provider shortages, transportation barriers, and socioeconomic challenges. Despite established efficacy in urban and academic settings, limited data exist on the feasibility and real-world outcomes of TMS implementation in rural healthcare settings. The purpose of this study is to highlight the feasibility …

Comparison Of Axillary Lymph Node Size In Cadavers With And Without A History Of Breast Cancer, Adam E. Davis, Harshita Yepuri, Julia Girgis, Sara Kurtovic, Celeste Pak, Erek Arsiniega, Jasdeep Singh, Michael B. Roberts, Shelley Dicecco

Research Day

Axillary lymph nodes play a critical role in breast cancer metastasis and staging. While imaging and surgical studies provide indirect assessments of nodal involvement, few investigations have directly compared lymph node size in breast cancer and non-cancer populations using cadaveric dissection. In this study, twenty-nine female cadavers, including eight with a history of breast cancer and twenty-one controls, were dissected to collect axillary lymph nodes from six anatomical chains: central, humeral, infraclavicular, parasternal, pectoral, and subscapular. Lymph node area (mm²) was measured, and statistical outliers (z ≥ 3) were excluded from analysis. Welch’s t-test was performed to compare overall lymph …

Genetic Architecture Of Coronary Atherosclerosis Across European, African, And Admixed American Populations Using All Of Us Research Program Data, Kensley Philemond, Jodeci L. Mitchell, Thomas J. Last

Research Day

Introduction:

Coronary atherosclerosis, the underlying pathology of most coronary artery disease, is characterized by the accumulation of lipid-rich plaques within the coronary arteries, leading to increased cardiovascular risk. Established genes such as LDLR highlight the importance of lipid metabolism in disease pathogenesis, yet population-specific genetic contributors in African and Admixed American populations remain poorly understood. Identifying additional genetic contributors may improve our understanding of disease mechanisms and support more equitable cardiovascular risk prediction tools.

Methods:

We analyzed Genome Wide Association Study (GWAS) summary statistics from the All of Us Research Program using the All-by-All Research Browser to identify genetic variants …

A Rare Case Of Suspected Mayer-Rokitansky-Küster-Hauser Syndrome: A Comparative Review Of Androgen Insensitivity Syndrome, Olivia G. Deloach, Caroline R. Kebberly, Zoë M. Rushetsky, Sreehitha Sanku, Mariah Smith, Marcel Castor

Research Day

Mayer–Rokitansky–Küster–Hauser (MRKH) syndrome and androgen insensitivity syndrome (AIS) are two distinct disorders of sexual development that can present with similar clinical features, including primary amenorrhea, an absent uterus, and typical female external genitalia.

We present the case of a 27-year-old female who died following a motor vehicle accident and was found to have congenital absence of the uterus, cervix, and upper vagina, consistent with MRKH syndrome. MRKH occurs in phenotypic females with normal ovarian function, whereas AIS presents similarly but occurs in genotypic males with absent Müllerian structures and no ovaries.

This case was identified incidentally during an autopsy at …

Many Genomes, One Disease: Genetic Risk Of Hidradenitis Suppurativa Across Ancestries, Sydney E. Williams, Nadine Belony, Thomas Last

Research Day

Introduction

Hidradenitis suppurativa (HS) is a chronic inflammatory disease of the folliculopilosebaceous unit affecting intertriginous areas including the axillae, groin, buttocks, and inframammary regions. It presents with recurrent painful nodules, abscesses, sinus tracts, and scarring, leading to substantial physical and psychosocial burden. Up to 40% of patients report severe quality-of-life impairment, with strong associations to depression and work disability. HS disproportionately affects individuals of African ancestry and demonstrates disparities in disease burden. Despite its clinical impact, the genetic architecture of HS remains incompletely defined, particularly across diverse populations. Although rare familial cases implicate γ-secretase pathway mutations, broader genetic contributors to …

Understanding The Genetic Basis Of Keloid Susceptibility Through Multi-Ancestry Genomic Studies, Nadine Belony, Sydney Williams, Thomas Last

Research Day

Introduction

Keloids are benign fibroproliferative skin tumors arising from dysregulated wound healing and characterized by excessive extracellular matrix deposition. Although nonmalignant, they are frequently associated with pain, pruritus, restricted mobility, and significant cosmetic disfigurement, resulting in substantial impairment in quality of life. The burden of keloid disease is not uniformly distributed across populations, with higher prevalence and severity observed among individuals of African ancestry, suggesting biologic contributors to disease susceptibility. Despite these disparities, mechanisms underlying pathologic scarring remain incompletely defined. Improved characterization of shared and ancestry-specific contributors may advance understanding of dermal fibrosis and support equitable dermatologic care.

Methods

We …

Exploration Of A Relationship Between The Activities Of Trail And 4’-Trifluoromethoxychalcone., Abigail C. Ernst

Undergraduate Theses

Cancer is the overgrowth of dysregulated or mutated cells that affects 1 in 3 Americans. Chalcones are natural products with many possible derivatives, such as 4’-trifluromethoxychalcone (4TF), developed in Dr. Krzysiak’s lab, which exhibit anticancer activity against cancer cell lines. Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) is a tumor surveillance cytokine that acts on two receptor types: death receptors and decoy receptors. One way cancer cells can become resistant to TRAIL is by upregulating decoy receptors and/or downregulating death receptors. In this study, MTS assays evaluated the potential relationship between TRAIL and 4TF that sensitizes A549 cells to TRAIL. The …

Vascular Burden Attenuates The Tdp-43-Tmem106b Pathological Relationship In Neurodegenerative Disease With And Without Alzheimer Disease Neuropathological Change, Matthew B. Dopler, Cole Corbett, Angelique D. Gonzalez, Ali Ghaseminejad-Bandpey, Mallory Keating, Kyra M. Clarke, Oluwaseun B. Ogunbona, Gladys Maestre, Sudha Seshadri, Shahroo Etemadmoghadam, Margaret E. Flanagan

School of Medicine Publications

TMEM106B, a lysosomal transmembrane protein, is a risk factor for neurodegenerative diseases, including Alzheimer disease (ad) and TDP-43 proteinopathies. TMEM106B pathology occurs in normal aging and is increased in TDP-43 proteinopathy but its role in dementia remains unclear. Cerebrovascular disease (CVD) is a driver and co-pathology of dementia, yet its contribution to TMEM106B accumulation in the context of TDP-43 and ad neuropathological changes (ADNC) has not been explored. We analyzed post-mortem human hippocampal sections spanning not-, low-, intermediate-, and high-ADNC. In secondary analyses, cases ≥65 years were stratified by TDP-43 immunopositivity and CVD severity; cases < 65 years were included to contextualize age-associated effects. TMEM106B immunoreactivity was quantified using digital pathology. Linear regression models demonstrated that age and sex (higher in females) were independent predictors of TMEM106B immunopositivity whereas Braak stage, CERAD-NP score, and Thal phase were not. The positive TDP-43-TMEM106B association was attenuated with increased CVD pathology severity, suggesting that vascular burden modifies this relationship. Sensitivity analyses restricted to LATE-NC attenuated several associations, indicating that pooled TDP-43 findings should be interpreted cautiously given possible disease heterogeneity. TMEM106B immunoreactivity was most strongly associated with age and sex, while vascular burden, rather than ADNC level, modified its relationship with TDP-43 proteinopathy.