Neurosciences Commons^™

Plasma Aβ42/40 Predicts Progression From Aβ-Amyloid Negative To Positive Pet Scans, Azadeh Feizpour, Vincent Doré, Pierrick Bourgeat, James D. Doecke, Rodrigo Canovas, Simon M. Laws, Tenielle Porter, Kun Huang, Christopher Fowler, Ralph N. Martins, Paul Maruff, Hamid R. Sohrabi, Michael W. Weiner, John C. Morris, Tammie L.S. Benzinger, Suzanne E. Schindler, Randall J. Bateman, Yan Li, Ovod Vitaliy, Larry Ward, Jurgen Mejan-Fripp, Colin L. Masters, Victor L. Villemagne, Christopher C. Rowe

Research outputs 2022 to 2026

Background The agreement between plasma Aβ42/40 and Aβ positron emission tomography (PET) is approximately 75 %, with ∼85 % of discrepancies due to positive plasma but negative PET results. It is unclear whether this reflects Aβ changes in plasma before PET-detectable. Objectives To assess the influence of Aβ42/40 positivity on risk of progression to Aβ PET positivity, and feasibility of using plasma Aβ42/40 tests to enrich a primary prevention trial. Design A prospective longitudinal cohort study. Setting Participants of Australian Imaging, Biomarkers and Lifestyle study (AIBL), Alzheimer’s Disease Neuroimaging Initiative (ADNI), and Open Access Series of Imaging Studies 3 (OASIS3). …

Exploring The Mechanisms Of Tanshinone Iia In The Treatment Of Intracranial Aneurysm Based On Network Pharmacology And Machine Learning, Wanqi Wang, Lois Balmer, Shaotao Weng

Research outputs 2022 to 2026

Background Intracranial aneurysm (IA) is a cerebrovascular disease with high mortality and limited treatment options. Tanshinone IIA (Tan IIA), a bioactive compound from Salvia miltiorrhiza , has shown vascular protective effects, but its mechanism in the treatment of IA remains unclear. Methods The GSE75436 dataset was used to identify differentially expressed genes (DEGs). Weighted gene co-expression network analysis (WGCNA) was performed to identify disease-related modules. IA targets were obtained from GeneCards and the Comparative Toxicogenomics Database (CTD). Potential targets of Tan IIA were predicted using TCMSP, SwissTargetPrediction, and SymMap. KEGG enrichment analysis was conducted for DEGs, WGCNA modules, disease-related genes, …

Prevalence Of Dementia In Selected Middle East And North Africa (Mena) Countries: A Systematic Review And Meta-Analysis, Mohsen Sedighi, Mohammad Hasan Shahabi, Alireza Amanollahi, Khurshid Alam, Soudabeh Shemehsavar, Zahra Shirzadi, Serena Sabatini, Ahmad R. Khatoonabadi, Matthew Prina, Akram A. Hosseini, Claire V. Burley, Jennifer Dunne, Simin Mahinrad, Iman Dajani, Ralph N. Martins, Blossom C.M. Stephan, Ali Chaari, Hamid R. Sohrabi

Research outputs 2022 to 2026

Data on dementia epidemiology in the Middle East and North Africa (MENA) region is limited. This systematic review and meta-analysis examined dementia prevalence across MENA. Databases were searched up to October 2024. Analyses were stratified by country and sex. Pooled prevalence was estimated using a random-effects model with a 95% confidence interval (CI). Fifty-two studies on the selected countries met inclusion criteria, covering 87,219 individuals with dementia from a total population of 1,045,908. The pooled prevalence was 12.16% (95% CI: 9.61–14.96) for the region and the Israel had the highest prevalence (17.00%), followed by Iran (13.20%), Turkey (11.40%), Saudi Arabia …

When Does Alzheimer's Disease Start? Plasma Aβ42/40 Assays Show Steep Changes At Aβ-Pet Centiloid 15, Mean Age Of 66 Years, Rodrigo Cánovas, Timothy Cox, Vincent Doré, Pierrick Bourgeat, Jurgen Fripp, Azadeh Feizpour, Rosita Shishegar, Christopher J. Fowler, Simon M. Laws, Tenielle Porter, Stephanie Rainey-Smith, Leslie M. Shaw, Randall J. Bateman, Yan Li, Ovod Vitaliy, Michael W. Weiner, John C. Morris, Tammie L.S. Benzinger, Suzanne E. Schindler, Akinori Nakamura, Takeshi Iwatsubo, Takeshi Ikeuchi, Takashi Kato, Paul Maruff, Hamid R. Sohrabi, Christopher C. Rowe, Ralph Martins, Colin L. Masters, James Doecke

Research outputs 2022 to 2026

Objective: Sporadic late-onset Alzheimer's disease (AD) is characterized by a long pre-clinical phase where amyloid-beta (Aβ) and tau begin to accumulate in the brain. The primary objective was to determine the age at which AD starts by finding the average population age when both positron emission tomography (PET) Aβ (Aβ-PET) and plasma Aβ42/40 become abnormal. Methods: Two high performance immunoprecipitation-mass spectrometry (IP-MS) assays (WashU/C2N and Shimadzu) were tested on samples from 1,450 participants who were diagnosed as cognitively unimpaired (CU), mild cognitive impairment (MCI), or AD-dementia across 4 international cohorts. Natural history modeling and trajectory analyses of the combined Aβ-PET …

Unraveling The Significance Of Fecal Microrna Profile In Alzheimer’S Disease, Kavisha Katuwawala, Prashant Bharadwaj, Ian Martins, B. G.D.N.K. De Silva, Vincent Ho, Asiri Dissanayake, Ralph N. Martins, W. M.A.D.Binosha Fernando

Research outputs 2022 to 2026

Alzheimer’s disease (AD), a complex neurodegenerative disorder characterised by progressive cognitive decline, affects millions globally. With no current cure, treatment focuses on symptom management and slowing disease progression. Early identification is therefore crucial. Fecal microRNA (miRNA) analysis is emerging as a promising non-invasive diagnostic tool. Evidence suggests that miRNAs present in fecal samples may regulate gene expression linked to AD pathology, impacting cellular functions and disease progression. Dietary factors critically influence gut microbiota composition and diversity, affecting brain health via the gut brain axis. Macronutrients such as carbohydrates, proteins, and fats modulate miRNA expression and gut microbiota, influencing AD risk. …

Gut Microbial Composition And Short-Chain Fatty Acid Metabolism In Cognitively Unimpaired Adults Stratified By Amyloid-Β Status, D. M.Sithara Dissanayaka, Thilini N. Jayasinghe, Hamid R. Sohrabi, Stephanie R. Rainey-Smith, Kevin Taddei, Colin L. Masters, Ralph N. Martins, W. M.A.D.Binosha Fernando

Research outputs 2022 to 2026

Short-chain fatty acids (SCFAs) produced by gut microbial fermentation influence host metabolism and neuroinflammatory processes implicated in Alzheimer’s disease (AD). However, the relationship between fecal SCFAs, microbial taxa, and cerebral amyloid-β (Aβ) burden in cognitively unimpaired individuals remains unclear. Fecal SCFAs were quantified using GC-MS, and microbial species were profiled by shotgun metagenomics in 87 participants. Associations between SCFAs, demographics, APOE ε4 status, and Aβ burden were tested using nonparametric statistics and multivariable regression. Microbial–SCFA links were evaluated using Spearman correlations and multivariate ordinations, with mediation analysis exploring potential indirect pathways. Acetate was the predominant SCFA and demonstrated the most …

Pain In People With Dementia Is A Significant Contributor To Increased Professional Caregiver Burden: Results Of An Observation Study, Kreshnik Hoti, Ipsit Vahia, Paola Chivers, Jeffery Hughes

Research outputs 2022 to 2026

Aim: To investigate the association between the presence of neuropsychological symptoms, professional caregiver burden and pain intensity.

Methods: Eleven neuropsychiatric symptoms reportedly associated with caregiver burden which are included within the PainChek® pain assessment tool were identified: aggressiveness, inappropriate behavior, distressed, verbally offensive, confusion, restlessness, pacing and wandering, crying, screaming, altered sleep and resisting care. A caregiver burden score based on binary scoring of the presence of these indicators was calculated (summative score range from 0 to 11). Generalized estimating equations were used to evaluate the relationships between (1) pain score and sum of caregiver indicators present and (2) pain …

The Associations Between Sleep Environment Factors And Sleep Health In Individuals Living With Neurological Conditions, Mitchell Turner, Laws, Madeline Griffiths, Travis Cruickshank

Research outputs 2022 to 2026

Objectives: To explore associations between air temperature and light in the sleeping environment and sleep health in individuals with neurological conditions. Methods: The sleep health of 46 individuals with neurological conditions (mean age 51.37 ± 14.24 years; 20 males, 26 females) was measured using the Sleep Health Index (SHI). Air temperature and light data were captured across seven days using a light/temperature data logger positioned next to the participant’s bed. Data recorded during the participants’ sleeping periods (determined using a sleep diary) were analyzed. Linear regression models were used to assess the associations between air temperature and light and sleep …

Loss Of The Maternal Effect Gene Nlrp2 Impairs Embryonic And Extra-Embryonic Development, Revealing A Novel Genetic Cause Of Congenital Anomalies†, Momal Sharif, Zahra Anvar, Imen Chakchouk, Sara H El-Dessouky, Roni Zemet, Eric C Kao, Wessam E Sharaf-Eldin, Ying-Wooi Wan, Zhandong Liu, Pengfei Liu, Michael Jochum, Ignatia B Van Den Veyver

Duncan NRI Faculty and Staff Publications

Maternal-effect genes (MEGs) play a crucial role in early mammalian development, and their dysfunction can lead to severe embryonic and extra-embryonic abnormalities. NLRP2, a MEG that encodes a subcortical maternal complex (SCMC) protein, has been implicated in preimplantation development, but its role after implantation remains underexplored. In this study, we investigated the developmental consequences of maternal Nlrp2 loss-of-function in a maternal knockout (KO) mouse model at embryonic day 11.5. Embryos derived from Nlrp2-KO females have abnormal yolk sac vasculature, increased embryonic resorption, craniofacial abnormalities, neural tube defects, and congenital heart defects. Placental architecture is disrupted with an altered junctional zone …

Exploring The Role Of Astrocyte System Xc– In Excitatory/Inhibitory Balance, Samantha Olivia Sutton

Theses - ALL

Astrocytes play a central role in maintaining excitatory/inhibitory (E/I) balance in the central nervous system by supporting intracellular glutathione (GSH) synthesis and regulating extracellular glutamate. System xc– (Sxc–), an obligate cystine/glutamate antiporter encoded by SLC7a11, couples the import of L-cystine with the export of L-glutamate. It is highly expressed throughout the cortex, hippocampus, striatum, and cerebellum, where its activity provides cystine—the rate-limiting substrate for cysteine-dependent GSH production—and contributes to ambient glutamatergic tone. Although global loss of Sxc– alters seizure threshold and redox homeostasis, whether these effects arise specifically from the loss of astrocytic Sxc– has remained unresolved. This thesis examined …

Discovery Of Small Molecules And A Druggable Groove That Regulate Dna Binding And Release Of The Ap-1 Transcription Factor Δfosb, Sean Mcneme, Yun Young Yim, Ashwani Kumar, Yi Li, Brandon Hughes, Corey Peyton St Romain, Galina Aglyamova, Jianping Chen, Nghi D Nguyen, Shanghua Fan, Gabriel S Stephens, Wen-Ning Zhao, Samantha Kruzshak, Molly Estill, Corrine Brener, Solange Tofani, Anil Kumar, Earnest P Chen, Nadeen Takatka, Alfred J Robison, Haiying Chen, Reid T Powell, Stephen J Haggarty, Clifford Stephan, Eric J Nestler, Jeannie Chin, Mischa Machius, Jia Zhou, Gabby Rudenko

Faculty, Staff and Students Publications

ΔFOSB, a member of the AP-1 family of transcription factors, mediates long-term neuroadaptations underlying drug addiction, seizure-related cognitive decline, dyskinesias, and several other chronic conditions. AP-1 transcription factors are notoriously difficult to modulate pharmacologically due to the absence of well-defined binding pockets. Here, we identify a novel site on ΔFOSB, located outside the DNA-binding cleft, that accommodates small molecules. We show that sulfonic acid-containing compounds bind to this site via an induced-fit mechanism, reorienting side chains critical for DNA binding, and that they may hinder the ΔFOSB bZIP α-helix from binding to the major groove of DNA. In vivo, direct …

Abnormalities In Sensorimotor Brain Function Are Related To Chronicity Of Low Back Pain, Jo Armour Smith, Rongwen Tain, Kelli G. Sharp, Laura M. Glynn, Linda R. Van Dillen, Jesse V. Jacobs, Steven C. Cramer

Physical Therapy Faculty Articles and Research

Maladaptive plasticity in the brain may contribute to chronic low back pain (LBP) and underlie the altered postural control of the lumbopelvic musculature that is evident in some individuals with LBP. We recently described an MRI-compatible leg-raise paradigm to measure brain activity associated with lumbopelvic postural control. The objective of this study was to compare brain function in young adults with and without a history of LBP and to determine relationships between brain function, pain, and postural control characteristics. We recruited 55 participants with a history of LBP, who were asymptomatic when studied, and 30 healthy controls. Postural control during …

Metabolomic Profiling Reveals Brain Lipid Alterations In Pex7-Deficient Models Of Rhizomelic Chondrodysplasia Punctata, Riya Sankhe, Meredith I Williams, Wedad Fallatah, Laura Mackay, Mary Layne Brown, Pranjali Bhagwat, Sarah H Elsea, Nancy Braverman, Michael F Wangler

Duncan NRI Faculty and Staff Publications

Rhizomelic chondrodysplasia punctata type 1 (RCDP1) is a peroxisomal disorder characterized by skeletal shortening, intellectual disability, seizures, cataracts, and reduced lifespans. RCDP1 is caused by biallelic loss-of-function variants in PEX7, which encodes a protein required for importing select enzymes into the peroxisome matrix, including those essential for ether lipid synthesis (e.g., plasmalogens) and the branched-chain fatty acid catabolism. Plasmalogen deficiency is a hallmark of RCDP1 and other peroxisomal disorders, including RCDP types 2-5 (RCDP2-5) and Zellweger spectrum disorders (ZSD). Here, we performed comprehensive metabolomic profiling of clinical samples from RCDP patients and Pex7-deficient mouse models. We identified profound …

Acute And Chronic Effects Of Neuroinflammation On Hippocampus And Anterior Cingulate Cortex Network Dynamics, Lauren A. Crew

UNLV Theses, Dissertations, Professional Papers, and Capstones

Neuroinflammation has emerged as a critical modulator of cognitive function and neural circuit dynamics, yet the distinct contributions of acute and chronic neuroinflammation to brain function remain poorly defined. This dissertation examines how inflammation independently alters large-scale neural activity and behavior, focusing on interactions between the hippocampus (HPC) and anterior cingulate cortex (ACC), regions essential for memory and executive processes. Using in vivo electrophysiological techniques in a rodent model, this study compares the effects of short-term (acute) and prolonged (chronic) neuroinflammatory states, induced via Poly I:C, on neural oscillations, regional coherence, and spatial coding. Findings reveal that even transient inflammation …

Seizures In Camp Settings, Sandra Shapiro, Taylor Gilman, Tamar Sternfield, Jolie Skivington

CompassPoint

Managing seizures in the summer camp environment presents unique challenges, requiring not only medical attention but also empathy and understanding from both peers and caregivers. Approximately 0.5–5% of children and adolescents will experience at least one afebrile seizure by adolescence and there is a 3.6% risk of experiencing at least one seizure in an 80-year-lifespan (Murphy et al., 1995 as cited in Wilfong, 2025). Recognizing how to support a child with seizures during the camp season is essential to promoting their safety and well-being while also ensuring they have a positive and inclusive camp experience.

Spike Timing Depended Plasticity Produces Unsupervised Learning Of Synergistic Muscle Feedback In A Synthetical Neural Network, Mark Allen Pupkiewicz

Dissertations and Theses

This study investigates how type Ia feedback from muscle spindles can be organized into groups representing agonistic muscle pairs through Spike Timing Dependent Plasticity (STDP). A single degree of freedom joint is actuated with four biologically modeled muscles forming two agonistic pairs. In order to emulate the sensory dynamics of biological muscle spindles, sensors in the model record the active length and velocity states of each muscle, the two primary factors eliciting type Ia afferent responses. In biological networks, synapses from Ia sensory neurons frequently activate interneurons representing agonistic muscle sources. This research investigates whether this organization can emerge in …

Functional Vs Anatomical Cortico-Striatal Connectivity In The Macaque Brain, Wei Tang, Megan E Monko, Zoe Liu, Ana M G Manea, Fernando A Ortega, Damyan Hart, Jason Zhou, Jan Zimmermann, Sarah R Heilbronner

Faculty, Staff and Students Publications

The cerebral cortex provides the main input to the striatum, constituting the first step in cortico-basal ganglia loops. Decades of careful anatomical tract-tracing research have established the exquisite topography of each cortical region's projection to the striatum in nonhuman primates. In parallel, neuroimaging research has demonstrated the relationship between cortico-striatal resting-state functional connectivity and specific cognitive, behavioral, psychiatric, and neurological states in humans. However, still unclear is the extent to which functional connectivity recapitulates the specific topographies of cortico-striatal anatomical connectivity. Here, we combined datasets of cortico-striatal anatomical and functional connectivity in macaques to determine the degree of overlap between …

Protein-Protein Interaction–Interfering Peptide Rescues Dysregulated Nmda Receptor Signaling, Robert E. Featherstone, Hongbin Li, Ameet S. Sengar, Karin E. Borgmann-Winter, Olya Melnychenko, Lindsey M. Crown, Ray L. Gifford, Felix Amirfathi, Anamika Banerjee, Aivi Tran, Krishna Parekh, Margaret Heller, Wenyu Zhang, Robert J. Gallop, Adam D. Marc, Pragya Komal, Michael W. Salter, Steven J. Siegel, Chang-Gyu Hahn

Farber Institute for Neuroscience Faculty Papers

The complex and heterogeneous genetic architecture of neuropsychiatric illnesses compels us to look beyond individual risk genes for therapeutic strategies and target the interactive dynamics and convergence of their protein products. A mechanistic substrate for convergence of synaptic neuropsychiatric risk genes are protein-protein interactions (PPIs) in the N-methyl-D-aspartate receptor (NMDAR) complex. NMDAR hypofunction in schizophrenia is associated with hypoactivity of Src kinase, resulting from convergent alterations in PPIs of Src with its partners. Of these, the association of Src with PSD-95, which inhibits the activity of this kinase in the NMDAR complex, is known to be increased in schizophrenia. Here, …

Super-Fast, Super-Early: High-Frequency Oscillations May Be A Prelude To Alzheimer's Dementia In Down Syndrome, Manuel Silva-Pérez, Jeannie Chin

Faculty, Staff and Students Publications

Alzheimer's disease (AD) dementia has near full penetrance in adults with Down syndrome (DS) and is strongly linked to late-onset myoclonic epilepsy in Down syndrome (LOMEDS). However, promising biomarkers of epileptogenicity, such as high-frequency oscillations (HFOs >250 Hz), have not been studied. This study is the first to use wideband polysomnography in DS to investigate if HFOs occurred and preceded AD dementia and LOMEDS. Methods: Wideband (0.1 to 500 Hz, 2048 Hz) polysomnography was performed using the international 10–20 system. HFOs were automatically detected during slow-wave sleep, followed by manual review. Results: Fourteen individuals with DS and five age-matched euploid …

Dopaminergic Regulation Of Aversive Motivation, Elaine M. Grafelman

Dissertations (1934 -)

We all experience adversity in our lives, and we must be able to effectively respond to these challenges in order to thrive. One way to respond to stressors is to change one’s behavior to cope with the stress. This can include escaping or avoiding the stressor, focusing effort to diminish the effect of the stressor, or other coping strategies such as drug use. In fact, stress is one of the principal triggers of relapse for those in the abstinence phase of a substance use disorder and it exacerbates a variety of other disorders. Therefore, it is critical to understand the …