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Articles 1 - 30 of 108

Full-Text Articles in Nervous System Diseases

Lovastatin Potentiates The Function Of Α7-Nicotinic Acetylcholine Receptors, Dmytro Isaev, Keun-Hang Susan Yang, Murat Oz May 2026

Lovastatin Potentiates The Function Of Α7-Nicotinic Acetylcholine Receptors, Dmytro Isaev, Keun-Hang Susan Yang, Murat Oz

Pharmacy Faculty Articles and Research

Background/Objectives: Statins are currently one of the most commonly used cholesterol-lowering drugs. In recent years, in addition to their well-known effects on the cardiovascular system, statins have been shown to exert beneficial effects in the progression of various neuropsychiatric and neurodegenerative diseases. Methods: In this study, the effects of lovastatin on the function of α7-nicotinic acetylcholine (nACh) receptors expressed in rat hippocampus and Xenopus oocytes were investigated. Results: In whole-cell patch clamp studies in hippocampal neurons, 21-day chronic (20 mg/kg), but not acute (20 min), lovastatin treatment caused significant potentiation of choline (a selective agonist for α7 nACh receptors)-induced currents …


Brain Delivery Of Antibody-Derived Biologicals For Alzheimer’S Disease: An Updated Narrative Review, Rachita K. Sumbria, Ruben J. Boado Apr 2026

Brain Delivery Of Antibody-Derived Biologicals For Alzheimer’S Disease: An Updated Narrative Review, Rachita K. Sumbria, Ruben J. Boado

Pharmacy Faculty Articles and Research

Antibodies directed against β-amyloid (Aβ) have been developed for the treatment of Alzheimer’s disease (AD). However, the in vivo central efficacy is reduced by the poor penetration of antibodies across the blood–brain barrier (BBB). In addition, these antibodies have been associated with adverse effects like amyloid-related imaging abnormalities. Thus, the development of new antibody-based therapies for AD with improved transport across the BBB may improve efficacy and reduce adverse effects. Antibodies targeting the BBB transferrin receptor (TfR) are able to cross the BBB through receptor-mediated transcytosis, producing a global distribution throughout the brain. Along the same line, bispecific antibodies directed …


Sedentary Behavior Modifies The Effect Of Balance Rehabilitation On Balance Discordance In Parkinson’S Disease, Franziska Albrecht, Sarah J. Conklin, Andrew Hooyman, Daniel S. Peterson, Jason K. Longhurst, Erika Franzén Apr 2026

Sedentary Behavior Modifies The Effect Of Balance Rehabilitation On Balance Discordance In Parkinson’S Disease, Franziska Albrecht, Sarah J. Conklin, Andrew Hooyman, Daniel S. Peterson, Jason K. Longhurst, Erika Franzén

Physical Therapy Faculty Articles and Research

Individuals with Parkinson’s disease (PD) often experience a misalignment between their perceived and actual balance ability, known as balance discordance, which has been associated with falls. We examined whether high-intensity balance and gait training (HiBalance) alters balance discordance in individuals with PD, and whether baseline sedentary behavior influences these changes. A secondary analysis examining pre- to post-intervention discordance changes of two HiBalance clinical trials (N = 97) using linear regression with interactions between sedentary behavior and pre-intervention discordance. The sample included two cohorts: one clinical and one research based. The model including sedentary behavior and its interaction with pre-intervention …


Using Diffusion Mri To Relate Hippocampal Subfield Microstructure To Delayed Verbal Memory In Cognitively Intact Individuals At Genetic Risk For Developing Alzheimer's Disease, Jennapher Lingo Vangilder, Andrew Hooyman, Sasha Hakhu, Kurt G. Schilling, Leland S. Hu, Yuxiang Zhou, Richard J. Caselli, Leslie C. Baxter, Scott C. Beeman Mar 2026

Using Diffusion Mri To Relate Hippocampal Subfield Microstructure To Delayed Verbal Memory In Cognitively Intact Individuals At Genetic Risk For Developing Alzheimer's Disease, Jennapher Lingo Vangilder, Andrew Hooyman, Sasha Hakhu, Kurt G. Schilling, Leland S. Hu, Yuxiang Zhou, Richard J. Caselli, Leslie C. Baxter, Scott C. Beeman

Physical Therapy Faculty Articles and Research

Intervention to delay the onset of Alzheimer's disease (AD) is an important treatment strategy but detecting at-risk individuals before significant disease progression remains challenging. This study evaluates the relationship between hippocampal microstructure and verbal cognition in cognitively intact older adults, focusing on the differences between APOΕ ε4 allele carriers and noncarriers. Participants (n = 41 noncarriers, 33 carriers) over 60 years old (mean ± SD: carriers 71 ± 6.6; noncarriers 71 ± 6.4 years) underwent diffusion-weighted magnetic resonance imaging (dMRI) and volumetric assessments. We assessed hippocampal structure, including microstructure, using Neurite Orientation Dispersion and Density Imaging (NODDI), diffusion tensor …


Multi-Modal Tensor Fusion For Alzheimer’S Disease Recognition, Mason Li, Tiffany Le, Jiajing Huang, Yuxin Wen Mar 2026

Multi-Modal Tensor Fusion For Alzheimer’S Disease Recognition, Mason Li, Tiffany Le, Jiajing Huang, Yuxin Wen

Engineering Faculty Articles and Research

Accurate and early diagnosis of Alzheimer’s disease (AD) is critical for effective intervention, disease monitoring, and patient care. Traditional diagnostic approaches rely on a single modality, such as clinical assessments, neuroimaging, or genetic markers, which may fail to capture the complex, multifaceted nature of AD. Multimodal learning has therefore been explored to integrate complementary information across data sources. However, conventional fusion strategies, including early feature concatenation and late decision-level fusion, often model modalities independently and fail to capture high-order cross-modal interactions. To address these limitations, we propose a multimodal tensor fusion network (MTFN) that integrates heterogeneous data sources, including visual …


Discordance Between Actual And Perceived Balance Ability Relates To Quality Of Life And Global Cognition In A Clinical Sample Of Parkinson Patients, Daniel S. Peterson, Jason K. Longhurst, Franziska Albrecht, Joanna Weller, Jennifer Vasquez, Myassar Zarif, Mark Gudesblatt, Andrew Hooyman Mar 2026

Discordance Between Actual And Perceived Balance Ability Relates To Quality Of Life And Global Cognition In A Clinical Sample Of Parkinson Patients, Daniel S. Peterson, Jason K. Longhurst, Franziska Albrecht, Joanna Weller, Jennifer Vasquez, Myassar Zarif, Mark Gudesblatt, Andrew Hooyman

Physical Therapy Faculty Articles and Research

Background

Misalignment between actual and perceived balance ability provides relevant information to understand functional deficits and fall risk. However, few studies have provided a continuous quantification of misalignment in neurological populations such as people with Parkinson's disease (PD).

Objective

Determine whether a continuous quantification of misalignment between actual and perceived balance ability, discordance, relates to functional outcomes such as quality of life and cognition.

Methods

Actual (gait velocity), and perceived (Activities of Balance Confidence) balance, cognition (measured via a computer-based cognitive assessment), and mobility-related quality of life were captured in a clinical sample of 95 people with PD. Primary outcomes …


Biomarkers In Alzheimer's Disease Clinical Trials: 2025, Amanda M. Leisgang Osse, Yadi Zhou, Jefferson W. Kinney, Andrew Hooyman, Ayan Sengupta, Jorge Fonseca, Aaron H. Burstein, Laura Nisenbaum, Howard M. Fillit, Feixiong Cheng, Jeffrey L. Cummings Feb 2026

Biomarkers In Alzheimer's Disease Clinical Trials: 2025, Amanda M. Leisgang Osse, Yadi Zhou, Jefferson W. Kinney, Andrew Hooyman, Ayan Sengupta, Jorge Fonseca, Aaron H. Burstein, Laura Nisenbaum, Howard M. Fillit, Feixiong Cheng, Jeffrey L. Cummings

Physical Therapy Faculty Articles and Research

Biomarkers play an important role in Alzheimer's disease (AD) clinical trials in several contexts of use, including defining trial eligibility and serving as outcome measures. Utilizing clinicaltrials.gov, a registry of clinical trials, we assessed biomarker usage across all active AD disease-targeted therapeutic (DTT) trials. Biomarkers are widely used in AD DTT trials, with 84% including a fluid, imaging, and/or digital biomarker, either as an inclusion criterion or as an outcome measure. In DTT trials, biomarkers were included in 83% of Phase 3 trials, 91% of Phase 2 trials, and 72% of Phase 1 trials. Biomarkers were used for trial inclusion …


Evaluating The Effect Of Ethnicity And Amyloid On Gait Speed In The Healthy Aging Brain Study-Health Disparities Study, Alexandra M. Reed, Andrew Hooyman, Edward Ofori, Sydney Y. Schaefer Dec 2025

Evaluating The Effect Of Ethnicity And Amyloid On Gait Speed In The Healthy Aging Brain Study-Health Disparities Study, Alexandra M. Reed, Andrew Hooyman, Edward Ofori, Sydney Y. Schaefer

Physical Therapy Faculty Articles and Research

Background

Many novel Alzheimer's disease (AD) biomarkers have been studied in non-Hispanic White populations, despite Hispanic/Latino adults being 1.5 times more likely to develop AD and receiving a later diagnosis. Equitable, accessible assessments are needed to identify individuals at risk earlier. While cognitive screening monitors early AD signs, neuropsychological tests are often inequitable across ethnicity, race, and other social determinants of health. However, we have shown that performance-based motor assessments may be less susceptible to demographic factors than memory tests, and may be more equitable for screening older adults. Gait speed has been linked to elevated amyloid in non-Hispanic White …


Hepatocyte-Specific Lrp1 Silencing Exacerbates Brain Amyloidosis Without Compensatory Ldl Receptor Family Involvement, Brian Carson, Josephine Chu, Devaraj V. Chandrashekar, Jerome Garcia, Rachita K. Sumbria, Derick Han Dec 2025

Hepatocyte-Specific Lrp1 Silencing Exacerbates Brain Amyloidosis Without Compensatory Ldl Receptor Family Involvement, Brian Carson, Josephine Chu, Devaraj V. Chandrashekar, Jerome Garcia, Rachita K. Sumbria, Derick Han

Pharmacy Faculty Articles and Research

Background

LDL receptor related protein 1 (LRP1) is a major hepatic receptor involved in lipoprotein metabolism, protease degradation, transmembrane receptor modulation, and clearance of excess protein, such as Aβ. Decreased expression of LRP1 due to liver injury can impair receptor-mediated clearance, increasing Aβ availability in the periphery. We investigated the effects of hepato-specific silencing of LRP1 on Aβ deposition in the brain. Additionally, other LDL family members (LRP5, LRP6, and LDLR) that may participate in Aβ clearance were monitored in the liver to ensure non-compensatory effects of LRP1 silencing.

Method

4-month-old male double transgenic (APP/PS1) AD mice were injected with …


The Mitochondria Is The Source Of Hepatic Amyloid Precursor Protein And Peripheral Amyloid Beta: Implications Of Alcohol-Induced Liver Steatosis In Alzheimer's Disease, Josephine Chu, Ross A. Steinberg, Brian Carson, Devaraj Venkatapura Chandrashekar, Rachita K. Sumbria, Derick Han Dec 2025

The Mitochondria Is The Source Of Hepatic Amyloid Precursor Protein And Peripheral Amyloid Beta: Implications Of Alcohol-Induced Liver Steatosis In Alzheimer's Disease, Josephine Chu, Ross A. Steinberg, Brian Carson, Devaraj Venkatapura Chandrashekar, Rachita K. Sumbria, Derick Han

Pharmacy Faculty Articles and Research

Background

Alcohol-induced liver injury occurs in the pericentral region of the liver and can induce mitochondrial remodeling and exacerbate Alzheimer's Disease (AD) progression. Subpopulations of mitochondria: general mitochondria (GM), peridroplet mitochondria (PDM) and endoplasmic reticulum(ER)-bound mitochondria (ERM) maintain cellular homeostasis via energy synthesis, lipid homeostasis, and regulation of intracellular calcium. Hepatic amyloid precursor protein (APP) is a source of peripheral amyloid beta (aB) and affects AD pathology in the brain. Understanding the localization and expression of hepatic APP in mitochondrial subpopulations are critical to understanding aB metabolism and may play a role in identifying a potential mechanism for metabolic dysfunction. …


Longitudinal Pharmacokinetic And Safety Studies Of An Antibody-Erythropoietin Fusion Protein For Alzheimer's Disease, Rudy Chang, Devaraj Venkatapura Chandrashekar, G. Chuli Roules, Nataraj Jagadeesan, Emi Iwasaki, Adenike Oyegbesan, Hayk Davtyan, Rachita K. Sumbria Dec 2025

Longitudinal Pharmacokinetic And Safety Studies Of An Antibody-Erythropoietin Fusion Protein For Alzheimer's Disease, Rudy Chang, Devaraj Venkatapura Chandrashekar, G. Chuli Roules, Nataraj Jagadeesan, Emi Iwasaki, Adenike Oyegbesan, Hayk Davtyan, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Erythropoietin (EPO) shows promise for Alzheimer's disease (AD) but has poor brain penetration, necessitating high doses that cause hematopoietic side effects. To improve brain delivery, EPO was fused to a transferrin receptor monoclonal antibody (TfRMAb), and this study evaluated the pharmacokinetics (PK), safety, and efficacy of repeated TfRMAb-EPO dosing in mice to further its preclinical development. C57BL/6J male mice (10 weeks old, n = 4–5/dose) received subcutaneous (SQ) low (1 mg/kg), mid (3 and 6 mg/kg), or high (20 mg/kg) TfRMAb-EPO doses for 4 weeks. The 1 mg/kg dose showed no adverse effects and resulted in sustained brain and plasma …


Comprehensive Descriptive Analysis Of Large Alzheimer's Disease Patient Cohorts, Ehsan Yaghmaei, Attallah Dillard, Mohammadreza Rezaei, Ahmad Razaei, Albert Pierce, Hongxia Lu, Eric Adams, Nikolay Todorov, Louis Ehwerhemuepha, Jianwei Zheng, Seyed Ahmad Sajjadi, Mohsen Bazargan, Cyril Rakovski Oct 2025

Comprehensive Descriptive Analysis Of Large Alzheimer's Disease Patient Cohorts, Ehsan Yaghmaei, Attallah Dillard, Mohammadreza Rezaei, Ahmad Razaei, Albert Pierce, Hongxia Lu, Eric Adams, Nikolay Todorov, Louis Ehwerhemuepha, Jianwei Zheng, Seyed Ahmad Sajjadi, Mohsen Bazargan, Cyril Rakovski

Mathematics, Physics, and Computer Science Faculty Articles and Research

Background

Precise estimates of the prevalence of Alzheimer's disease (AD), the distribution of demographic characteristics, comorbidities, treatment plans, insurance types, cost of treatment and survival probabilities at various time points are crucially important to advancing our understanding and for improving future AD research studies.

Objective

We analyzed two of the largest and high-quality medical databases, Oracle EHR Real-World Data and IQVIA. The results provide the most complete description of the AD patients in the US.

Methods

We present high-accuracy summary statistics of many important variables related to AD patients. Proportions, means and 95% confidence intervals were provided for all levels …


Twenty Minutes Of Corsi Block Tapping Task Training Does Not Improve Mental Rotation In Adults With Stroke, Sarah A. Kettlety, Giuliet L. Kibler, Andrew Hooyman, Christina K. Holl, Sydney Y. Schaefer, Kristan A. Leech Oct 2025

Twenty Minutes Of Corsi Block Tapping Task Training Does Not Improve Mental Rotation In Adults With Stroke, Sarah A. Kettlety, Giuliet L. Kibler, Andrew Hooyman, Christina K. Holl, Sydney Y. Schaefer, Kristan A. Leech

Physical Therapy Faculty Articles and Research

Background: Visuospatial function is commonly impaired post-stroke and is associated with motor learning and recovery. A single, twenty-minute Corsi Block Tapping Task (CBTT) training session improved visuospatial function in young neurotypical adults; however, it is unclear whether this training would improve visuospatial function in adults with stroke.

Objective: To understand if a single, twenty-minute CBTT training session improved visuospatial function in adults with stroke compared to a no-training control group of adults with stroke.

Methods: Participants post-stroke were assigned to one of two groups. The training group completed twenty minutes of computerized CBTT training. The control group completed a survey …


Predictive Gene Expression Signatures For Alzheimer's Disease Using Post-Mortem Brain Tissue, Ashley Duche, Oliver Tan, Andrius Baskys, Rachita K. Sumbria, Moom R. Roosan Oct 2025

Predictive Gene Expression Signatures For Alzheimer's Disease Using Post-Mortem Brain Tissue, Ashley Duche, Oliver Tan, Andrius Baskys, Rachita K. Sumbria, Moom R. Roosan

Pharmacy Faculty Articles and Research

Background: Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-beta (Aβ) plaques and tau protein aggregates in the brain. These pathological features manifest in specific regions, but mechanisms rendering some areas more susceptible to early AD-related changes remain poorly understood. To address this, we developed predictive gene expression signatures to explore molecular mechanisms underlying regional vulnerability to AD pathology.

Methods: Post-mortem brain tissues from participants of the Religious Orders Study and Memory and Aging Project (ROSMAP), Mayo Clinic, and Mount Sinai Brain Bank (MSBB) were used to derive gene expression signatures from six brain regions affected at varying …


The 9th Annual Lafora Science Symposium: A Rare Epilepsy Community Makes Progress Towards Clinical Readiness, Meredith I. Williams, Katherine J. Donahue, Pascual Sanz, Souad Messahel, Jose M. Serratosa, Jordi Duran, Roberto Michelucci, Lorenzo Muccioli, Antonio Delgado-Escueta, Viet-Hong Nguyen, Berge A. Minassian, Matthew S. Gentry Aug 2025

The 9th Annual Lafora Science Symposium: A Rare Epilepsy Community Makes Progress Towards Clinical Readiness, Meredith I. Williams, Katherine J. Donahue, Pascual Sanz, Souad Messahel, Jose M. Serratosa, Jordi Duran, Roberto Michelucci, Lorenzo Muccioli, Antonio Delgado-Escueta, Viet-Hong Nguyen, Berge A. Minassian, Matthew S. Gentry

Pharmacy Faculty Articles and Research

Lafora disease (LD) is a fatal childhood progressive myoclonus epilepsy and glycogen storage disease that is caused by recessive mutations in either EPM2A or EPM2B. The hallmarks of LD are cytoplasmic, aberrant glycogen-like aggregates, called Lafora bodies (LBs), that drive disease progression. The 9th Annual Lafora Science Symposium was held in San Diego, California and brought together over 70 researchers, clinicians, academic trainees, and friends and family members of patients with LD and 80 attendees joined virtually. This symposium focused primarily on international collaborations for therapeutic development and biomarker identification and strategies for preparing the Lafora community for upcoming …


Clinical Value Of Chatgpt For Epilepsy Presurgical Decision-Making: Systematic Evaluation Of Seizure Semiology Interpretation, Yaxi Luo, Meng Jiao, Neel Fotedar, Jun-En Ding, Ioannis Karakis, Vikram R. Rao, Melissa Asmar, Xiaochen Xian, Orwa Aboud, Yuxin Wen, Jack J. Lin, Fang-Ming Hung, Hai Sun, Felix Rosenow, Feng Liu May 2025

Clinical Value Of Chatgpt For Epilepsy Presurgical Decision-Making: Systematic Evaluation Of Seizure Semiology Interpretation, Yaxi Luo, Meng Jiao, Neel Fotedar, Jun-En Ding, Ioannis Karakis, Vikram R. Rao, Melissa Asmar, Xiaochen Xian, Orwa Aboud, Yuxin Wen, Jack J. Lin, Fang-Ming Hung, Hai Sun, Felix Rosenow, Feng Liu

Engineering Faculty Articles and Research

Background: For patients with drug-resistant focal epilepsy, surgical resection of the epileptogenic zone (EZ) is an effective treatment to control seizures. Accurate localization of the EZ is crucial and is typically achieved through comprehensive presurgical approaches such as seizure semiology interpretation, electroencephalography (EEG), magnetic resonance imaging (MRI), and intracranial EEG (iEEG). However, interpreting seizure semiology is challenging because it heavily relies on expert knowledge. The semiologies are often inconsistent and incoherent, leading to variability and potential limitations in presurgical evaluation. To overcome these challenges, advanced technologies like large language models (LLMs)—with ChatGPT being a notable example—offer valuable tools for …


Effect Of Chronic Alcohol Feeding Using The Lieber-Decarli Diet On Alzheimer’S Disease Pathology In Tg2576 Mice, Devaraj V. Chandrashekar, Nataraj Jagadeesan, Tamara Abdullah, Rudy Chang, Ross A. Steinberg, Frankey Sanchez, Elias Khal, Joshua Yang, David H. Cribbs, Derick Han, Rachita K. Sumbria Mar 2025

Effect Of Chronic Alcohol Feeding Using The Lieber-Decarli Diet On Alzheimer’S Disease Pathology In Tg2576 Mice, Devaraj V. Chandrashekar, Nataraj Jagadeesan, Tamara Abdullah, Rudy Chang, Ross A. Steinberg, Frankey Sanchez, Elias Khal, Joshua Yang, David H. Cribbs, Derick Han, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Background: Chronic alcohol drinking is a modifiable risk factor for Alzheimer’s disease (AD), but underlying mechanisms remain poorly understood. Most studies of alcohol feeding to AD mice have utilized young mice and delivered alcohol in drinking water without controlling nutritional intake.

Objective: To study the impact of Lieber-DeCarli (LDC) liquid alcohol diet, which balances nutritional intake, on AD pathology of aged Tg2576 and wild-type (WT) mice, which is unexplored.

Methods: 13-month-old male and female Tg2576 or WT mice were fed LDC diet (5% ethanol or control) for six weeks (n = 11-13/group). Exploration (open-field test) and spatial reference memory …


Tdp43 Autoregulation Gives Rise To Dominant Negative Isoforms That Are Tightly Controlled By Transcriptional And Post-Translational Mechanisms, Megan M. Dykstra, Kaitlin Weskamp, Nicolás B. Gómez, Jacob Waksmacki, Elizabeth Tank, M. Rebecca Glineburg, Allison Snyder, Emile Pinarbasi, Michael Bekier, Xingli Li, Morgan R. Miller, Jen Bai, Shameena Shahzad, Neha Nedumaran, Clare Wieland, Corey Stewart, Sydney Willey, Nikolas Grotewold, Jonathon Mcbride, John J. Moran, Aditya V. Suryakumar, Michael Lucas, Peter M. Tessier, Michael Ward, Peter K. Todd, Sami J. Barmada Jan 2025

Tdp43 Autoregulation Gives Rise To Dominant Negative Isoforms That Are Tightly Controlled By Transcriptional And Post-Translational Mechanisms, Megan M. Dykstra, Kaitlin Weskamp, Nicolás B. Gómez, Jacob Waksmacki, Elizabeth Tank, M. Rebecca Glineburg, Allison Snyder, Emile Pinarbasi, Michael Bekier, Xingli Li, Morgan R. Miller, Jen Bai, Shameena Shahzad, Neha Nedumaran, Clare Wieland, Corey Stewart, Sydney Willey, Nikolas Grotewold, Jonathon Mcbride, John J. Moran, Aditya V. Suryakumar, Michael Lucas, Peter M. Tessier, Michael Ward, Peter K. Todd, Sami J. Barmada

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The nuclear RNA-binding protein TDP43 is integrally involved in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Previous studies uncovered N-terminal TDP43 isoforms that are predominantly cytosolic in localization, prone to aggregation, and enriched in susceptible spinal motor neurons. In healthy cells, however, these shortened (s)TDP43 isoforms are difficult to detect in comparison to full-length (fl)TDP43, raising questions regarding their origin and selective regulation. Here, we show that sTDP43 is created as a by-product of TDP43 autoregulation and cleared by nonsense-mediated RNA decay (NMD). sTDP43-encoding transcripts that escape NMD are rapidly degraded post-translationally via the proteasome …


Two-Year Follow-Up Of Gait And Postural Control Following Initiation Of Recombinant Human Tripeptidyl Intracerebroventricular Enzyme Replacement Therapy In Two Atypical Cln2 Patients, Rahul Soangra, Marybeth Grant-Beuttler, Harriet Chang, Raymond Y. Wang Jan 2025

Two-Year Follow-Up Of Gait And Postural Control Following Initiation Of Recombinant Human Tripeptidyl Intracerebroventricular Enzyme Replacement Therapy In Two Atypical Cln2 Patients, Rahul Soangra, Marybeth Grant-Beuttler, Harriet Chang, Raymond Y. Wang

Physical Therapy Faculty Articles and Research

Neuronal ceroid lipofuscinosis type 2 (CLN2) is a rapidly progressive neurodegenerative disorder leading to premature mortality. Ambulatory CLN2 patients typically receive standard of care treatment through biweekly intracerebroventricular (ICV) enzyme replacement therapy (ERT) involving recombinant human tripeptidyl peptidase 1, known as cerliponase alfa (Brineura®, Biomarin Pharmaceuticals). This study longitudinally assessed the impact of ICV cerliponase alfa ERT on gait, and postural control across a two-year span in two siblings diagnosed with atypical CLN2 disease. Both participants, ID01 (18 years and 8 months old at enrollment) and ID02 (13 years and 3 months old at enrollment), exhibited symptomatic characteristics …


Bile Duct Ligation-Induced Cirrhosis Does Not Alter The Blood-Brain Barrier Permeability To Sucrose In Rats, Mohammad K. Miah, Ulrich Bickel, Reza Mehvar Dec 2024

Bile Duct Ligation-Induced Cirrhosis Does Not Alter The Blood-Brain Barrier Permeability To Sucrose In Rats, Mohammad K. Miah, Ulrich Bickel, Reza Mehvar

Pharmacy Faculty Articles and Research

Contradictory results have been reported about the effects of liver diseases on the blood-brain barrier (BBB) permeability to markers. For instance, both an increase and no change in the BBB permeability to BBB markers sodium fluorescein and Evans blue have been reported in experimental cholestasis induced by bile duct ligation (BDL) in rats. These contradictory effects might be due to inherent limitations of these markers and/or methodological issues. Here, we investigated the time course of the impact of BDL in rats on BBB permeability using a recently developed stable isotope labeled marker [13C]sucrose, which is expected to be …


Rings Of Power: Controlling Sod Mimic Activity By The Addition Of Pyridine Rings Within The Pyridinophane Scaffold, Katherine J. Smith, Timothy M. Schwartz, David M. Freire, Cameron Bowers, Sarah K. Dunn, Jackson F. Bonnell, Magy A. Mekhail, Giridhar Akkaraju, Kayla N. Green Dec 2024

Rings Of Power: Controlling Sod Mimic Activity By The Addition Of Pyridine Rings Within The Pyridinophane Scaffold, Katherine J. Smith, Timothy M. Schwartz, David M. Freire, Cameron Bowers, Sarah K. Dunn, Jackson F. Bonnell, Magy A. Mekhail, Giridhar Akkaraju, Kayla N. Green

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Superoxide dismutase enzymes are a major defense against superoxide, which is a potent reactive oxygen species. Misregulation of reactive oxygen species and subsequent neuronal damage are etiological hallmarks of neurodegenerative disease. Macrocyclic small molecules have offered inroads toward functional SOD1 mimics. Herein, we report a series of five tetra-aza macrocyclic RPy2N2 ligands, varied by 4-position substitution of the pyridine ring with both electron-donating (R = OMe) and withdrawing groups (R = Cl, I, and CF3) to offer the first comparison to well-studied RPyN3 congeners and other mimics in the literature. New ligands …


Discordance Between Balance Ability And Perception Is Associated With Falls In Parkinson’S Disease: A Coordinated Analysis, Jason K. Longhurst, Andrew Hooyman, Merrill R. Landers, Martina Mancini, Erika Franzén, Breiffni Leavy, Hanna Johansson, Daniel Peterson Nov 2024

Discordance Between Balance Ability And Perception Is Associated With Falls In Parkinson’S Disease: A Coordinated Analysis, Jason K. Longhurst, Andrew Hooyman, Merrill R. Landers, Martina Mancini, Erika Franzén, Breiffni Leavy, Hanna Johansson, Daniel Peterson

Physical Therapy Faculty Articles and Research

Background: The congruence or discordance between actual and perceived balance ability has been proposed to be linked to functional outcomes such as falls. However, gaps remain in our ability to quantify discordance, and its relationship to relevant outcomes.

Objective: To investigate a novel quantification of concordance/discordance between balance performance and perception and determine the relationship to falls among people with Parkinson’s disease (PwPD).

Methods: Data from 244 PwPD were aggregated from 5 previously conducted studies. Variables extracted included age, sex, Activities-Specific Balance Confidence scale (ABC; perceived balance), Timed Up and Go (TUG; balance performance), Movement Disorder Society Unified Parkinson Disease …


Multimodal Mixing Convolutional Neural Network And Transformer For Alzheimer’S Disease Recognition, Junde Chen, Yun Wang, Adnan Zeb, M. D. Suzauddola, Yuxin Wen Sep 2024

Multimodal Mixing Convolutional Neural Network And Transformer For Alzheimer’S Disease Recognition, Junde Chen, Yun Wang, Adnan Zeb, M. D. Suzauddola, Yuxin Wen

Engineering Faculty Articles and Research

Early recognition of Alzheimer’s disease (AD) and its precursor state, mild cognitive impairment (MCI), is pivotal in interrupting the progression of the disease and providing suitable treatment. Recent development in deep learning techniques has drawn great research attention for improving the efficacy of AD recognition. However, numerous current methods solely utilize data from a single auxiliary domain, limiting their ability to harness valuable intrinsic insights from multiple domains. To cope with the challenge, this paper is devoted to establishing an innovative multimodal medical data fusion model, termed as MMDF, to perform Alzheimer’s disease recognition. Multimodal data including clinical records and …


Stress Granule Formation Helps To Mitigate Neurodegeneration, M. Rebecca Glineburg, Evrim Yildirim, Nicolas Gomez, Genesis Rodriguez, Jaclyn Pak, Xingli Li, Christopher Altheim, Jacob Waksmacki, Gerald M. Mcinerney, Sami J. Barmada, Peter K. Todd Aug 2024

Stress Granule Formation Helps To Mitigate Neurodegeneration, M. Rebecca Glineburg, Evrim Yildirim, Nicolas Gomez, Genesis Rodriguez, Jaclyn Pak, Xingli Li, Christopher Altheim, Jacob Waksmacki, Gerald M. Mcinerney, Sami J. Barmada, Peter K. Todd

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Cellular stress pathways that inhibit translation initiation lead to transient formation of cytoplasmic RNA/protein complexes known as stress granules. Many of the proteins found within stress granules and the dynamics of stress granule formation and dissolution are implicated in neurodegenerative disease. Whether stress granule formation is protective or harmful in neurodegenerative conditions is not known. To address this, we took advantage of the alphavirus protein nsP3, which selectively binds dimers of the central stress granule nucleator protein G3BP and markedly reduces stress granule formation without directly impacting the protein translational inhibitory pathways that trigger stress granule formation. In Drosophila and …


Hepatic Lrp-1 Plays An Important Role In Amyloidosis In Alzheimer's Disease Mice: Potential Role In Chronic Heavy Alcohol Feeding, Devaraj V. Chandrashekar, G. Chuli Roules, Nataraj Jagadeesan, Urvashi R. Panchal, Adenike Oyegbesan, Oghenetega E. Imiruaye, Hai Zhang, Jerome Garcia, Kamaljit Kaur, Sanda Win, Tin A. Than, Neil Kaplowitz, Moom R. Roosan, Derick Han, Rachita K. Sumbria Jun 2024

Hepatic Lrp-1 Plays An Important Role In Amyloidosis In Alzheimer's Disease Mice: Potential Role In Chronic Heavy Alcohol Feeding, Devaraj V. Chandrashekar, G. Chuli Roules, Nataraj Jagadeesan, Urvashi R. Panchal, Adenike Oyegbesan, Oghenetega E. Imiruaye, Hai Zhang, Jerome Garcia, Kamaljit Kaur, Sanda Win, Tin A. Than, Neil Kaplowitz, Moom R. Roosan, Derick Han, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Background

Hepatic lipoprotein receptor-related protein 1 (LRP-1) plays a central role in peripheral amyloid beta (Aβ) clearance, but its importance in Alzheimer's disease (AD) pathology is understudied. Our previous work showed that intragastric alcohol feeding to C57BL/6 J mice reduced hepatic LRP-1 expression which correlated with significant AD-relevant brain changes. Herein, we examined the role of hepatic LRP-1 in AD pathogenesis in APP/PS1 AD mice using two approaches to modulate hepatic LRP-1, intragastric alcohol feeding to model chronic heavy drinking shown by us to reduce hepatic LRP-1, and hepato-specific LRP-1 silencing.

Methods

Eight-month-old male APP/PS1 mice were fed ethanol or …


A Single-Center, Assessor-Blinded, Randomized Controlled Clinical Trial To Test The Safety And Efficacy Of A Novel Brain-Computer Interface Controlled Functional Electrical Stimulation (Bci-Fes) Intervention For Gait Rehabilitation In The Chronic Stroke Population, Piyashi Biswas, Lucy Dodakian, Po T. Wang, Christopher A. Johnson, Jill See, Vicky Chan, Cathy Chou, Wendy Lazouras, Alison L. Mckenzie, David J. Reinkensmeyer, Danh V. Nguyen, Steven C. Cramer, An H. Do, Zoran Nenadic Jun 2024

A Single-Center, Assessor-Blinded, Randomized Controlled Clinical Trial To Test The Safety And Efficacy Of A Novel Brain-Computer Interface Controlled Functional Electrical Stimulation (Bci-Fes) Intervention For Gait Rehabilitation In The Chronic Stroke Population, Piyashi Biswas, Lucy Dodakian, Po T. Wang, Christopher A. Johnson, Jill See, Vicky Chan, Cathy Chou, Wendy Lazouras, Alison L. Mckenzie, David J. Reinkensmeyer, Danh V. Nguyen, Steven C. Cramer, An H. Do, Zoran Nenadic

Physical Therapy Faculty Articles and Research

Background

In the United States, there are over seven million stroke survivors, with many facing gait impairments due to foot drop. This restricts their community ambulation and hinders functional independence, leading to several long-term health complications. Despite the best available physical therapy, gait function is incompletely recovered, and this occurs mainly during the acute phase post-stroke. Therapeutic options are limited currently. Novel therapies based on neurobiological principles have the potential to lead to long-term functional improvements. The Brain-Computer Interface (BCI) controlled Functional Electrical Stimulation (FES) system is one such strategy. It is based on Hebbian principles and has shown promise …


Combined Use Of Donepezil And Memantine Increases The Probability Of Five-Year Survival Of Alzheimer’S Disease Patients, Ehsan Yaghmaei, Hongxia Lu, Louis Ehwerhemuepha, Jianwei Zheng, Sidy Danioko, Ahmad Rezaie, Seyed Ahmad Sajjadi, Cyril Rakovski May 2024

Combined Use Of Donepezil And Memantine Increases The Probability Of Five-Year Survival Of Alzheimer’S Disease Patients, Ehsan Yaghmaei, Hongxia Lu, Louis Ehwerhemuepha, Jianwei Zheng, Sidy Danioko, Ahmad Rezaie, Seyed Ahmad Sajjadi, Cyril Rakovski

Mathematics, Physics, and Computer Science Faculty Articles and Research

Background

Alzheimer’s disease (AD) is the most common neurodegenerative disease. Studying the effects of drug treatments on multiple health outcomes related to AD could be beneficial in demonstrating which drugs reduce the disease burden and increase survival.

Methods

We conducted a comprehensive causal inference study implementing doubly robust estimators and using one of the largest high-quality medical databases, the Oracle Electronic Health Records (EHR) Real-World Data. Our work was focused on the estimation of the effects of the two common Alzheimer’s disease drugs, Donepezil and Memantine, and their combined use on the five-year survival since initial diagnosis of AD patients. …


Examining The Diagnostic Accuracy Of A Novel Performance-Based Test For Alzheimer's Disease Screening, A. M. Reed, K. Duff, L. E. Dibble, S. S. Paul, Andrew Hooyman, S. Y. Schaefer May 2024

Examining The Diagnostic Accuracy Of A Novel Performance-Based Test For Alzheimer's Disease Screening, A. M. Reed, K. Duff, L. E. Dibble, S. S. Paul, Andrew Hooyman, S. Y. Schaefer

Physical Therapy Faculty Articles and Research

Affordable, rapid methods for identifying mild Alzheimer’s disease (AD) are needed. A simple, brief performance-based test involving the learning of functional upper-extremity movements has been developed and is associated with AD pathology and functional decline. However, its specificity to AD relative to other neurodegenerative diseases that present with motor impairment is unknown. This study examined whether this novel test could distinguish between 34 participants diagnosed with mild AD (Clinical Dementia Rating Scale = 0.5-1) from 23 participants with mild-to-moderate Parkinson’s disease (PD) (Hoehn & Yahr = 2-3) using Receiver Operating Characteristic analysis of secondary data from two separate clinical trials. …


Apigenin Alleviates Autistic-Like Stereotyped Repetitive Behaviors And Mitigates Brain Oxidative Stress In Mice, Petrilla Jayaprakash, Dmytro Isaev, Keun-Hang Susan Yang, Rami Beiram, Murat Oz, Bassem Sadek Apr 2024

Apigenin Alleviates Autistic-Like Stereotyped Repetitive Behaviors And Mitigates Brain Oxidative Stress In Mice, Petrilla Jayaprakash, Dmytro Isaev, Keun-Hang Susan Yang, Rami Beiram, Murat Oz, Bassem Sadek

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Studying the involvement of nicotinic acetylcholine receptors (nAChRs), specifically α7-nAChRs, in neuropsychiatric brain disorders such as autism spectrum disorder (ASD) has gained a growing interest. The flavonoid apigenin (APG) has been confirmed in its pharmacological action as a positive allosteric modulator of α7-nAChRs. However, there is no research describing the pharmacological potential of APG in ASD. The aim of this study was to evaluate the effects of the subchronic systemic treatment of APG (10–30 mg/kg) on ASD-like repetitive and compulsive-like behaviors and oxidative stress status in the hippocampus and cerebellum in BTBR mice, utilizing the reference drug aripiprazole (ARP, 1 …


Adolescent Marijuana Use And The Contribution To The Development Of Schizophrenia, Jocelyn Spandikow Apr 2024

Adolescent Marijuana Use And The Contribution To The Development Of Schizophrenia, Jocelyn Spandikow

Psychology Student Papers and Posters

Schizophrenia is an often debilitating mental condition that has become a popular topic of psychological research in recent years. Current research examines the correlation between drug use, genetics, and environment on the development of schizophrenia. Research looks at the structure of the brain in individuals with and without schizophrenia. However, research has failed to look at the specific correlation between marijuana use in adolescent youth and the developmental impact on the brain, including in the development of schizophrenia. The legalization of many recreational drugs, including marijuana, has come to fruition in recent years. This has raised concerns over adolescent access …