Neurosciences Commons^™

Dissecting Ms4a4a Function In Microglia And Its Role In Alzheimer’S Disease Pathogenesis, Emma Pascal Danhash

Arts & Sciences Graduate Student Theses and Dissertations

Genome-wide association studies have begun to uncover the complex genetic architecture of Alzheimer's disease (AD). Expression of many AD risk loci is enriched in microglia, the resident immune cells of the brain. Common variants near the MS4A gene family have been associated with AD risk and altered soluble triggering receptor expressed on myeloid cells 2 (sTREM2) levels in the cerebrospinal fluid (CSF). MS4A4A is a microglial gene that encodes a tetraspan membrane protein that regulates anti-inflammatory responses in macrophages. However, the mechanism by which MS4A4A contributes to microglial function and AD pathogenesis remains unknown. In this dissertation, I leveraged a …

Sarcopenic Obesity And Dementia Risk: Primary Associations And Landmark Analyses Of Muscle Strength And Body Composition Trajectories, Zhongyang Guan, Blossom C.M. Stephan, Lorenzo M. Donini, Justyna Godos, Giuseppe Grosso, Leticia Radin Pereira, Carla M. Prado, Carlos J. Toro-Huamanchumo, Jonathan C.K. Wells, Marc Sim, Mario Siervo

Research outputs 2022 to 2026

Background and aims: Sarcopenic obesity (SO) has been proposed as a risk factor for cognitive impairment. Yet evidence is inconsistent and often limited by heterogeneous definitions and lack of longitudinal assessments. This study aimed to examine associations of SO with all-cause and subtype-specific dementia, and to assess dose–response patterns and how longitudinal changes in body composition and muscle strength relate to dementia risk. Methods: We included 489,972 adults (mean age 56.5 ± 8.1 years) followed for a median of 13.6 years. SO was defined using the Sarcopenic Obesity Global Leadership Initiative (SOGLI) criteria. Cox models estimated hazard ratios (HRs) for …

Extending Genome-Wide Association Studies To Admixed Cohorts With High Degrees Of Relatedness, Taotao Tan, Alejandra Vergara-Lope, José Jaime Martínez-Magaña, Nirav N Shah, Yi-Sian Lin, Kai Yuan, Jaime Berumen, Jesus Alegre-Díaz, Pablo Kuri-Morales, Roberto Tapia-Conyer, Joel Gelenter, Janitza L Montalvo-Ortiz, Wei Zhou, Jason M Torres, Elizabeth G Atkinson

Duncan NRI Faculty and Staff Publications

Admixed populations comprise a large portion of the human population worldwide, but are often excluded from genome-wide association studies (GWASs) due to analytic challenges. Our group developed Tractor, a local-ancestry-informed GWAS tool designed for admixed samples that produces accurate ancestry-specific effect sizes and boosts the discovery power to identify ancestry-enriched loci. However, Tractor operates under an assumption of unrelated samples. Here, to address this gap, we propose Tractor-Mix, which allows for well-calibrated association studies in datasets containing admixed samples with relatedness. Extensive simulations show that this method is competitive with other state-of-the-art approaches that do not produce ancestry-specific results. Empirical …

A Blended Genome And Exome Sequencing Method Captures Genetic Variation In An Unbiased And Cost-Effective Manner, Toni A Boltz, Benjamin B Chu, Matthew Defelice, Calwing Liao, Julia M Sealock, Robert Ye, Jacqueline I Goldstein, Lerato Majara, Jack M Fu, Susan K Service, Lingyu Zhan, Sarah E Medland, Sinéad B Chapman, Simone Rubinacci, Jonna L Grimsby, Tamrat Abebe, Melkam Alemayehu, Fred K Ashaba, Elizabeth G Atkinson, Tim B Bigdeli, Amanda B Bradway, Harrison Brand, Lori B Chibnik, Samuel Deluca, Ana M Diaz-Zuluaga, Abebaw Fekadu, Michael Gatzen, Bizu Gelaye, Stella Gichuru, Marissa L Gildea, Toni C Hill, Hailiang Huang, Kalyn M Hubbard, Wilfred E Injera, Roxanne James, Moses Joloba, Christopher Kachulis, Phillip R Kalmbach, Rogers Kamulegeya, Gabriel Kigen, Soyeon Kim, Nastassja Koen, Edith K Kwobah, Joseph Kyebuzibwa, Seungmo Lee, Niall J Lennon, Penelope A Lind, Esteban A Lopera-Maya, Johnstone Makale, Serghei Mangul, Justin Mcmahon, Pierre Mowlem, Henry Musinguzi, Rehema M Mwema, Noeline Nakasujja, Carter P Newman, Lethukuthula L Nkambule, Conor R O'Neil, Ana Maria Olivares, Catherine M Olsen, Linnet Ongeri, Sophie J Parsa, Adele Pretorius, Shengying Qin, Raj Ramesar, Faye L Reagan, Chiara Sabatti, Jacquelyn A Schneider, Welelta Shiferaw, Christine Stevens, Anne Stevenson, Erik Stricker, Rocky E Stroud, Jessie Tang, Megan Townsend, David Whiteman, Mary T Yohannes, Mingrui Yu, Kai Yuan, Dickens Akena, Lukoye Atwoli, Symon M Kariuki, Karestan C Koenen, Charles R J C Newton, Dan J Stein, Solomon Teferra, Zukiswa Zingela, Carlos N Pato, Michele T Pato, Carlos Lopez-Jaramillo, Nelson B Freimer, Roel A Ophoff, Loes M Olde Loohuis, Michael E Talkowski, Benjamin M Neale, Daniel P Howrigan, Alicia R Martin

Duncan NRI Faculty and Staff Publications

Here we developed and deployed the blended genome exome (BGE) method, a DNA library approach that generates low-pass whole-genome (1–4× mean depth) and deep whole-exome (30–40× mean depth) data in a single sequencing run. BGE is cost-effective, empowers most genomic discoveries possible with deep whole-genome sequencing and captures global common single-nucleotide polymorphism diversity. We applied BGE to sequence >53,000 samples from the PUMAS Project (Populations Underrepresented in Mental Illness Associations Studies), including African, African American and Latin American populations. Imputed genotypes showed high concordance with Illumina Global Screening Array calls (R2 ≥ 95% for minor allele frequency ≥1%; …

Musical Training Increases Anticipatory Responding And Predictive Control In Sequence Learning, Li Ann Leow, Jarrad Lum, Sara Johnson, Emily Corti, Welber Marinovic

Research outputs 2022 to 2026

Musicians demonstrate advantages in acquiring motor sequences, showing faster learning and better explicit sequence knowledge than non-musicians. However, it is unclear whether this advantage extends beyond acquisition to the consolidation phase, which is when newly learned skills stabilize and become resistant to interference. Additionally, while interference from executing competing motor tasks is well-established, less is known about whether purely sensory information presented after learning can disrupt consolidation of a bimodal motor sequence. We investigated how post-acquisition sensory interference affects performance of a learned audio-visual sequence, and whether musical training moderates this vulnerability. Participants first learned an explicit sequence in a …

Hippo Signaling Regulates Cuticle Pigmentation And Dopamine Metabolism In Drosophila, Shelley B Gibson, Samantha L Deal, Ye-Jin Park, Bo Sun, Yanyan Qi, Jung-Wan Mok, Hyung-Lok Chung, Hongjie Li, Shinya Yamamoto

Duncan NRI Faculty and Staff Publications

Pigmentation plays multiple important roles in development, physiology and evolution. Melanization of the insect cuticle requires dopamine as a precursor of melanin and involves key enzymes in dopamine biosynthesis including Tyrosine hydroxylase (TH) and Dopa decarboxylase (Ddc). Some studies have hinted that disruption of the evolutionarily conserved Hippo signaling pathway, which has been primarily studied in the context of tissue growth, may lead to changes in cuticle pigmentation in the fruit fly Drosophila melanogaster. However, to our knowledge, there have not been any systematic investigations into their potential mechanistic links. In this study, we identified that all genes that comprise …

Engagement Of Understudied Populations As Community Change: The South Texas Adrc Model, Gladys E. Maestre, Neela K. Patel, Rosa V. Pirela, Robin C. Hilsabeck, Kendra Stine, Neyra García, Roberto Reyes, Omar Oropeza, Cristian Maestre, Jesus D. Melgarejo, Sarah Williams-Blangero, Ney Alliey Rodriguez

School of Medicine Publications

Many populations experiencing the highest burdens of Alzheimer's disease and related dementias remain understudied, in part because traditional recruitment and retention models are insufficient to support sustained engagement. The Outreach, Recruitment, and Engagement Core (OREC) of the South Texas Alzheimer's Disease Research Center reconceptualized participant recruitment as a long-term system change in a Hispanic-majority, urban–rural region. OREC institutionalizes shared power through community advisory governance, aligns research protocols with local lived realities (through patient navigators, community health workers/promotores, and decentralized access points), and employs a data-driven feedback loop for continuous improvement. In 1 year, 46 outreach events touched 10,134 individuals (71% …

Loss Of Pleasure (Anhedonia): A Sex-Dependent, Cross-Species Consequence Of Unpredictable Signals To The Perinatal Brain, Anna M. Zhou, Madison R. Tetzlaff, Laura M. Glynn, Curt A. Sandman, Hal S. Stern, Tallie Z. Baram, Elysia Poggi Davis

Psychology Faculty Articles and Research

Reward seeking is an essential component of human behavior. Anhedonia (reduced motivation for and pleasure in reward) is a core feature of several mental illnesses. Early life adversity associates with later impairments in reward behaviors and related psychopathology; however, specific aspects of early adversity that lead to disrupted reward behaviors are unknown. Capitalizing on evidence that unpredictable signals to the developing brain constitute adversity and influence neurodevelopment, we examined whether exposure to perinatal unpredictable maternal signals associated with diminished reward responsivity, and probed causality using experiments in mice. We analyzed a longitudinal human study (N=158 mother/child dyads) and a …

Infant Hippocampal And Amygdala Volume In An Observational Follow-Up From A Randomized Clinical Trial For Maternal Prenatal Depression, Catherine H. Demers, Benjamin L. Hankin, Lillybelle K. Deer, Robert J. Gallop, Mercedes Hoeflich Haase, M. Camille Hoffman, Martin A. Styner, Nancy K. Grote, Elysia Poggi Davis

Psychology: Data Sets

Prenatal maternal depression may have intergenerational effects on offspring brain development, with potential socioemotional consequences. In an observational follow-up of a randomized clinical trial of a prenatal depression intervention (the CARE Project; ClinicalTrials.gov NCT03011801), brain development and subsequent negative emotionality were examined among 109 infants born to mothers randomized during pregnancy to brief interpersonal psychotherapy or enhanced usual care. These data include MRI-derived hippocampal and amygdala volumes at approximately 6 weeks of age and a laboratory-based assessment of infant negative emotionality at 6 months.

Resulting Publication: Infant hippocampal and amygdala volume in an observational follow-up from a randomized clinical trial …

Editorial: Emerging Treatment Approaches For Substance Use Disorders, David Martinez Garza, Ilya O. Blokhin, Jonathan Brett, Ihsan Salloum

School of Medicine Publications

No abstract provided.

Online Decoding Of Rat Self-Paced Locomotion Speed From Eeg Using Recurrent Neural Networks, Alejandro De Miguel, Nelson Totah, Uri Maoz

Psychology Faculty Articles and Research

Objective. Accurate and reliable neural decoding of locomotion holds promise for advancing clinical applications such as rehabilitation and prosthetic control, as well as for understanding neural correlates of action. Recent studies have demonstrated successful decoding of locomotion kinematics across species in motorized treadmill settings. However, efforts to decode locomotion speed directly and continuously in more natural contexts—where pace is self-selected rather than externally imposed—are scarce, and those that exist generally achieve only modest accuracy and require intracranial implants. Here, we aim to decode self-paced locomotion speed non-invasively and continuously using cortex-wide electroencephalography (EEG) recordings from rats. Approach. We introduce an …

Extracellular Vesicle-Mediated Transfer Of Gsdme-Nt Pores As A Mechanism Of Inflammation Propagation, Bifeng Xiao

Master's Theses

Inflammasomes are multiprotein complexes that initiate inflammatory signaling through activation of caspase-1, cytokine maturation, and cleavage of Gasdermin D (GSDMD). Cleaved GSDMD forms membrane pores that contribute to cytokine release and pyroptotic cell death. Recent evidence suggests that extracellular vesicles (EVs) may facilitate the intercellular transfer of inflammatory mediators. This study investigated whether GSDMD N-terminal fragment (GSDMD-NT) associates with EV-enriched fractions and contributes to inflammation propagation. Doxycycline-inducible HeLa cells expressing FLAG-tagged GSDMD-NT were used to generate EV-enriched fractions. Western blot analysis detected GSDMD-NT-associated material within EV fractions, while EV marker analysis supported successful enrichment of EV-associated material. Exposure of recipient …

The Effects Of Anti-Parkinsonian Medications On Bone Mineral Density: A Systematic Review, Mícheál Ó Breasail, Motaz B. El-Leissy, Karan P. Singh, Matthew Smith, Jakub Mesinovic, Marc Sim, Andrew Evans, David Blacker, Saman Heshmat, Neil Mahant, Christian Girgis, Peter R. Ebeling, Ayse Zengin

Research outputs 2022 to 2026

IntroductionParkinson's disease (PD) is associated with elevated fracture risk, particularly at the hip. Antiparkinsonian medications have also been associated with increased fracture risk; although their direct effects on bone mineral density (BMD) remains unclear.ObjectiveInvestigate whether antiparkinsonian medications influence BMD.MethodsA systematic search of four databases (Embase, MEDLINE, APA PsycINFO, Web of Science) was conducted up to 24/11/2025 using terms related to PD, antiparkinsonian medications and bone.ResultsA total of 748 records were identified, with 543 screened following deduplication. Fourteen studies underwent full-text review, of which seven met inclusion criteria. Three studies assessed bone mineral content or surrogate measures at non-standard sites (hand …

Cognitive Decline In Dutch-Type Hereditary And Sporadic Cerebral Amyloid Angiopathy: A 5-Year Follow-Up Study, Rosemarie Van Dort, Vera C.J. Van Stek-Smits, Sanne E. Schriemer, Reinier G.J. Van Der Zwet, Manon R. Schipper, Sabine Voigt, Ellen P. Hart, Vandhana Easwaran, Hamid R. Sohrabi, Kevin Taddei, Samantha L. Gardener, Ralph N. Martins, Steven M. Greenberg, Matthias J.P. Van Osch, Marianne A.A. Van Walderveen, Marieke J.H. Wermer, Ellis S. Van Etten

Research outputs 2022 to 2026

Introduction: Cerebral amyloid angiopathy (CAA) is associated with cognitive impairment, but its longitudinal course of cognitive decline remains unclear. We investigated domain-specific cognitive trajectories in Dutch-type hereditary (D-CAA) and sporadic CAA (sCAA) to compare patterns and rates of decline. Methods: We included 181 participants – 93 D-CAA mutation carriers (59 without, 34 with prior intracerebral hemorrhage [ICH]) and 88 with sCAA (57 without, 31 with ICH) – who underwent annual neuropsychological assessment. Longitudinal change in global cognition, memory, processing speed, and executive function was analyzed using linear mixed models. Results: Over 5 years, cognitive decline was subtle but measurable. Memory …

Statistics Of Natural Scenes Shape Contextual Modulation In The Visual Cortex, Jiakun Fu, Suhas Shrinivasan, Luca Baroni, Zhuokun Ding, Paul G Fahey, Paweł A Pierzchlewicz, Nikos Karantzas, Kayla Ponder, Rachel Froebe, Lydia Ntanavara, Taliah Muhammad, Konstantin F Willeke, Eric Wang, Zhiwei Ding, Dat Tran, Stelios Papadopoulos, Saumil Patel, Jacob Reimer, Alexander S Ecker, Xaq Pitkow, Jan Antolik, Fabian H Sinz, Ralf M Haefner, Andreas S Tolias, Katrin Franke

Faculty, Staff and Students Publications

Vision is context dependent, with neuronal responses shaped not only by local features but also by surrounding visual input. While classical studies, using grating stimuli, show that iso-oriented surrounds suppress responses more than orthogonal surrounds, the role of contextual modulation under natural stimulus conditions remains less clear. Using recordings from mouse primary visual cortex (V1), we trained convolutional neural network models to predict neuronal responses to natural images and synthesized surround stimuli that selectively suppressed or facilitated responses to optimal center inputs. In vivo experiments confirmed these predictions. Facilitatory surrounds resembled naturalistic continuations of the optimal center stimulus, consistent with …

Predicting Accumulation And Age At Onset Of Amyloid-Β From Genetic Risk And Resilience For Alzheimer's Disease, Eleanor K. O'Brien, Timothy Cox, Shane Fernandez, Pierrick Bourgeat, Tenielle Porter, Ben Goudey, James D. Doecke, Colin L. Masters, Jurgen Fripp, Kwangsik Nho, Victor L. Villemagne, Carlos Cruchaga, Christopher C. Rowe, Andrew J. Saykin, Vincent Doré, Simon M. Laws

Research outputs 2022 to 2026

Background: Accumulation of brain amyloid beta (Aβ), a key pathological hallmark of Alzheimer's disease (AD), begins decades before cognitive symptoms. Being able to predict the risk of Aβ accumulation, or the age at which Aβ exceeds a critical threshold, may enable intervention to delay or prevent onset of AD. Methods: Using published genome-wide association studies (GWASs), we developed polygenic scores (PGS) for AD risk (PGSrisk) and resilience (PGSresilience), and tested whether these predicted (i) if an individual is an Aβ accumulator (‘Accumulator Status’), and (ii) in accumulators, the age at which brain Aβ exceeds a 20 centiloid (CL) threshold (‘Age …

Neuroprotective Effects Of Sorghum Polyphenol In Alzheimer’S Disease: In Vitro And In Silico Analyses, Rasheed A. Abdulraheem, Ralph N. Martins, Rajapandiyan Krishnamoorthy, Mohammad A. Alshuniaber, Prashant Bharadwaj, Zhaoyu Li, Ranil Coorey, Vijay Jayasena, Stuart K. Johnson, W. M.A.D.Binosha Fernando

Research outputs 2022 to 2026

Background/Objective: Accumulation of amyloid-beta (Aβ) senile plaques in the human brain is a major hallmark of Alzheimer’s disease (AD), which manifests as progressive decline in memory and cognitive functions and currently lacks effective disease-modifying therapies. Emerging evidence demonstrates that polyphenol-rich plant foods are potential complementary therapies for AD. Methods: In this study, we investigated crude polyphenol extracts (CPEs) and purified polyphenol extracts (PPEs) from three sorghum genotypes for their ability to inhibit Aβ42-induced toxicity in MC-65 cells. Thioflavin T fluorescence, cell viability, mitochondrial function, oxidative stress assays, and Western blotting, along with RNA sequencing and computational analyses, were used to …

Antibiotic Administration After Previable Preterm Prelabor Rupture Of Membranes Is Associated With Prolonged Latency, Alexandra L Hammerquist, Alexander M Saucedo, Selina L Bowler, Mohan Pammi, Catherine Eppes, Ignatia Van Den Veyver, Michael D Jochum, Enrico R Barrozo

Duncan NRI Faculty and Staff Publications

Introduction: While antibiotics have been shown to increase the interval to delivery between rupture of membranes and delivery (latency) and improve neonatal outcomes after viable preterm prelabor rupture of membranes (PPROM), this has not been well investigated in the previable PPROM population. We aimed to investigate the association between antenatal antibiotics and latency following previable PPROM. Secondarily, we examined various maternal and neonatal outcomes. We hypothesized that the administration of antibiotics would prolong latency in pregnancies with previable PPROM.

Methods: Single-center retrospective cohort study that included pregnancies diagnosed with previable PPROM between 140/7 and 216/7 and delivered between 2012 and …

Challenge-Based Ex Vivo Immune Profiling Reveals Stimulus-Dependent Peripheral Immune Reprogramming In Alzheimer's Disease, C. A. Naranjo-Galvis, Jovanny Zabaleta, Ney Alliey Rodriguez, Luisa Matilde Salamanca-Duque

School of Medicine Publications

Altered immune function is increasingly recognized as a contributor to Alzheimer's disease (AD); however, it remains unclear whether peripheral immune alterations reflect constitutive inflammation or stimulus-dependent changes in immune responsiveness. Addressing this distinction is critical for understanding immune dysregulation in neurodegenerative diseases. In this study, we applied a challenge-based ex vivo immune profiling approach to characterize functional immune responsiveness in patients with AD and in cognitively healthy older adults. Peripheral blood mononuclear cells were exposed to defined innate, antigenic, and mitogenic stimuli, and cytokine and β-amyloid (Aβ) responses were quantified in culture supernatants. Diagnosis-by-stimulus interaction effects were assessed using generalized …

Patient Activation Measures Among Individuals With Epilepsy: A Cross-Sectional Study Of An Arabic-Speaking Population, Ghada M. Abbas, Abeer A. Khoja, Haythum O. Tayeb, Nagham S. Alsolaimani, Ibrahim M. Aldurayhim, Saher F. Alqarni

Neurosciences

Objectives: To examine patient activation levels among Arabic-speaking adults with epilepsy and to explore their associations with selected clinical and sociodemographic variables.

Methods: We conducted a cross-sectional study of 109 adult patients with confirmed epilepsy between December 2023 and October 2025. Data were collected during outpatient clinic visits, with additional information obtained through telephone contact when necessary. A sample size estimate indicated that at least 96 participants were required to achieve 80% statistical power. Patient activation was assessed using the validated Arabic version of the 13-item Patient Activation Measure (PAM-13). The variables examined included seizure type, medication regimen (monotherapy versus …