Life Sciences Commons^™

Comparing Cognitive Tests And Smartphone-Based Assessment In 2 Us Community-Based Cohorts., Ileana De Anda-Duran, Preeti Sunderaraman, Edward Searls, Shirine Moukaled, Xuanyi Jin, Zachary Popp, Cody Karjadi, Phillip H Hwang, Huitong Ding, Sherral Devine, Ludy C Shih, Spencer Low, Honghuang Lin, Vijaya B Kolachalama, Lydia Bazzano, David J Libon, Rhoda Au

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

BACKGROUND: Smartphone-based cognitive assessments have emerged as promising tools, bridging gaps in accessibility and reducing bias in Alzheimer disease and related dementia research. However, their congruence with traditional neuropsychological tests and usefulness in diverse cohorts remain underexplored.

METHODS AND RESULTS: A total of 406 FHS (Framingham Heart Study) and 59 BHS (Bogalusa Heart Study) participants with traditional neuropsychological tests and digital assessments using the Defense Automated Neurocognitive Assessment (DANA) smartphone protocol were included. Regression models investigated associations between DANA task digital measures and a neuropsychological global cognitive

CONCLUSIONS: Our findings demonstrate that smartphone-based cognitive assessments exhibit concurrent validity with a …

Jun Upregulation Drives Aberrant Transposable Element Mobilization, Associated Innate Immune Response, And Impaired Neurogenesis In Alzheimer’S Disease, Chiara Scopa, Samantha Barnada, Maria Cicardi, Mo Singer, Davide Trotti, Marco Trizzino

Farber Institute for Neuroscience Faculty Papers

Adult neurogenic decline, inflammation, and neurodegeneration are phenotypic hallmarks of Alzheimer's disease (AD). Mobilization of transposable elements (TEs) in heterochromatic regions was recently reported in AD, but the underlying mechanisms are still underappreciated. Combining functional genomics with the differentiation of familial and sporadic AD patient derived-iPSCs into hippocampal progenitors, CA3 neurons, and cerebral organoids, we found that the upregulation of the AP-1 subunit, c-Jun, triggers decondensation of genomic regions containing TEs. This leads to the cytoplasmic accumulation of HERVK-derived RNA-DNA hybrids, the activation of the cGAS-STING cascade, and increased levels of cleaved caspase-3, suggesting the initiation of programmed cell death …

Bisphenol-A And Phthalate Metabolism In Children With Neurodevelopmental Disorders, T Peter Stein, Margaret D Schluter, Robert A Steer, Xue Ming

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

BACKGROUND: The etiology of autism spectrum (ASD) and Attention Deficit/Hyperactivity (ADHD) disorders are multifactorial. Epidemiological studies have shown associations with environmental pollutants, such as plasticizers. This study focused on two of these compounds, the Bisphenol-A (BPA) and Diethylhexyl Phthalate (DEHP). The major pathway for BPA and DEHP excretion is via glucuronidation. Glucuronidation makes insoluble substances more water-soluble allowing for their subsequent elimination in urine.

HYPOTHESIS: Detoxification of these two plasticizers is compromised in children with ASD and ADHD. Consequently, their tissues are more exposed to these two plasticizers.

METHODS: We measured the efficiency of glucuronidation in three groups of children, …

Sleep Problems In Old Age: Metabotropic Glutamate Receptor To The Rescue, Sho Inami, Dinis J.S. Afonso, Kyunghee Koh

Farber Institute for Neuroscience Faculty Papers

No abstract provided.

Probing The Role Of Astrocytes In The Pathology Of Fragile X Syndrome With Human Stem Cells, Baiyan Ren

Theses & Dissertations

Fragile X syndrome (FXS) is an X-linked neurodevelopmental disorder related to intellectual disability and the most common monogenic cause of autism spectrum disorder. FXS is mainly caused by an expansion of CGG repeats in the 5’-untranslated region of fragile X mental retardation 1 (FMR1) gene, leading to the loss of expression of fragile X mental retardation protein (FMRP). Astrocytes are the most abundant glial cells in the central nervous system (CNS). Loss of FMRP in astrocytes has been found to contribute to structural and functional synaptic deficits in the Fmr1-KO mouse model. The contribution of human astrocytes, however, to the …

Differential Activation Of Frontoparietal Attention Networks By Social And Symbolic Spatial Cues, Andrew D. Engell, Lauri Nummenmaa, Nikolaas N. Oosterhof, Richard N. Henson, James V. Haxby, Andrew J. Calder

Andrew D. Engell

Perception of both gaze-direction and symbolic directional cues (e.g. arrows) orient an observer’s attention toward the indicated location. It is unclear, however, whether these similar behavioral effects are examples of the same attentional phenomenon and, therefore, subserved by the same neural substrate. It has been proposed that gaze, given its evolutionary significance, constitutes a ‘special’ category of spatial cue. As such, it is predicted that the neural systems supporting spatial reorienting will be different for gaze than for non-biological symbols. We tested this prediction using functional magnetic resonance imaging to measure the brain’s response during target localization in which laterally …

Distinct Patterns Of Default Mode And Executive Control Network Circuitry Contribute To Present And Future Executive Function In Older Adults, Christopher A. Brown, Frederick A. Schmitt, Charles D. Smith, Brian T. Gold

Neuroscience Faculty Publications

Executive function (EF) performance in older adults has been linked with functional and structural profiles within the executive control network (ECN) and default mode network (DMN), white matter hyperintensities (WMH) burden and levels of Alzheimer's disease (AD) pathology. Here, we simultaneously explored the unique contributions of these factors to baseline and longitudinal EF performance in older adults. Thirty-two cognitively normal (CN) older adults underwent neuropsychological testing at baseline and annually for three years. Neuroimaging and AD pathology measures were collected at baseline. Separate linear regression models were used to determine which of these variables predicted composite EF scores at baseline …

Antibodies In The Diagnosis, Prognosis, And Prediction Of Psychotic Disorders., Thomas A Pollak, Jonathan P Rogers, Robert G Nagele, Mark Peakman, James M Stone, Anthony S David, Philip Mcguire

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Blood-based biomarker discovery for psychotic disorders has yet to impact upon routine clinical practice. In physical disorders antibodies have established roles as diagnostic, prognostic and predictive (theranostic) biomarkers, particularly in disorders thought to have a substantial autoimmune or infective aetiology. Two approaches to antibody biomarker identification are distinguished: a "top-down" approach, in which antibodies to specific antigens are sought based on the known function of the antigen and its putative role in the disorder, and emerging "bottom-up" or "omics" approaches that are agnostic as to the significance of any one antigen, using high-throughput arrays to identify distinctive components of the …

Als Mutations Of Fus Suppress Protein Translation And Disrupt The Regulation Of Nonsense-Mediated Decay, Marisa Kamelgarn, Jing Chen, Lisha Kuang, Huan Jin, Edward J. Kasarskis, Haining Zhu

Toxicology and Cancer Biology Faculty Publications

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease characterized by preferential motor neuron death. Approximately 15% of ALS cases are familial, and mutations in the fused in sarcoma (FUS) gene contribute to a subset of familial ALS cases. FUS is a multifunctional protein participating in many RNA metabolism pathways. ALS-linked mutations cause a liquid–liquid phase separation of FUS protein in vitro, inducing the formation of cytoplasmic granules and inclusions. However, it remains elusive what other proteins are sequestered into the inclusions and how such a process leads to neuronal dysfunction and degeneration. In this study, we developed …

Motivators For Alzheimer's Disease Clinical Trial Participation, Shoshana H. Bardach, Sarah D. Holmes, Gregory A. Jicha

Graduate Center for Gerontology Faculty Publications

Background

Alzheimer’s disease (AD) research progress is impeded due to participant recruitment challenges. This study seeks to better understand, from the perspective of individuals engaged in clinical trials (CTs), research motivations.

Methods

Participants, or their caregivers, from AD treatment and prevention CTs were surveyed about research motivators.

Results

The 87 respondents had a mean age of 72.2, were predominantly Caucasian, 55.2% were male, and 56.3% had cognitive impairment. An overwhelming majority rated the potential to help themselves or a loved one and the potential to help others in the future as important motivators. Relatively few respondents were motivated by free …

Treated Hypothyroidism Is Associated With Cerebrovascular Disease But Not Alzheimer's Disease Pathology In Older Adults, Willa D. Brenowitz, Fang Han, Walter A. Kukull, Peter T. Nelson

Pathology and Laboratory Medicine Faculty Publications

Thyroid hormone (TH) disease is common among older adults and is associated with cognitive impairment. However, pathologic correlates are not well understood. We studied pathologic and clinical factors associated with hypothyroidism, the most common form of TH disease, in research subjects seen annually for clinical evaluations at U.S. Alzheimer’s Disease Centers. Thyroid disease and treatment status were assessed during clinician interviews. Among autopsied subjects, there were 555 participants with treated hypothyroidism and 2,146 with no known thyroid disease; hypothyroidism was associated with severe atherosclerosis (OR=1.35 95% CI: 1.02, 1.79) but not Alzheimer’s disease (AD) pathologies (amyloid plaques or neurofibrillary tangles). …

Baseline White Matter Hyperintensities And Hippocampal Volume Are Associated With Conversion From Normal Cognition To Mild Cognitive Impairment In The Framingham Offspring Study., Katherine J Bangen, Sarah R Preis, Lisa Delano-Wood, Philip A Wolf, David J Libon, Mark W Bondi, Rhoda Au, Charles Decarli, Adam M Brickman

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

INTRODUCTION: We examined associations between magnetic resonance imaging (MRI) markers of cerebrovascular disease and neurodegeneration with mild cognitive impairment (MCI) diagnosis at baseline and conversion from normal cognition to MCI at follow-up.

METHODS: Framingham Offspring participants underwent brain MRI and neuropsychological assessment at baseline (n=1049) and follow-up (n=561). Participants were classified at baseline and at follow-up as cognitively normal or MCI using sensitive neuropsychological criteria. White matter hyperintensity (WMH) volume, covert brain infarcts, hippocampal volume, and total cerebral brain volume were quantified.

RESULTS: Baseline measures of WMH and hippocampal volume were associated with MCI status cross-sectionally and also with conversion …

Only The Human Brain Has The Cognitive Capacity For Jealousy, Donatella Marazziti

Animal Sentience

Jealousy is exclusively a human phenomenon because nonhuman animals lack the brain structures regulating the higher processes underlying jealousy.

Autonomic Dysreflexia After Spinal Cord Injury: Systemic Pathophysiology And Methods Of Management, Khalid C. Eldahan, Alexander G. Rabchevsky

Physiology Faculty Publications

Traumatic spinal cord injury (SCI) has widespread physiological effects beyond the disruption of sensory and motor function, notably the loss of normal autonomic and cardiovascular control. Injury at or above the sixth thoracic spinal cord segment segregates critical spinal sympathetic neurons from supraspinal modulation which can result in a syndrome known as autonomic dysreflexia (AD). AD is defined as episodic hypertension and concomitant baroreflex-mediated bradycardia initiated by unmodulated sympathetic reflexes in the decentralized cord. This condition is often triggered by noxious yet unperceived visceral or somatic stimuli below the injury level and if severe enough can require immediate medical attention. …

Physical Aggressiveness And Gray Matter Deficits In Ventromedial Prefrontal Cortex, David S. Chester, Donald R. Lynam, Richard Milich, C. Nathan Dewall

Psychology Faculty Publications

What causes individuals to hurt others? Since the famous case of Phineas Gage, lesions of the ventromedial prefrontal cortex (VMPFC) have been reliably linked to physically aggressive behavior. However, it is unclear whether naturally-occurring deficits in VMPFC, among normal individuals, might have widespread consequences for aggression. Using voxel based morphometry, we regressed gray matter density from the brains of 138 normal female and male adults onto their dispositional levels of physical aggression, verbal aggression, and sex, simultaneously. Physical, but not verbal, aggression was associated with reduced gray matter volume in the VMPFC and to a lesser extent, frontopolar cortex. Participants …

A Customized Quantitative Pcr Microrna Panel Provides A Technically Robust Context For Studying Neurodegenerative Disease Biomarkers And Indicates A High Correlation Between Cerebrospinal Fluid And Choroid Plexus Microrna Expression, Wang-Xia Wang, David W. Fardo, Gregory A. Jicha, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

MicroRNA (miRNA) expression varies in association with different tissue types and in diseases. Having been found in body fluids including blood and cerebrospinal fluid (CSF), miRNAs constitute potential biomarkers. CSF miRNAs have been proposed as biomarkers for neurodegenerative diseases; however, there is a lack of consensus about the best candidate miRNA biomarkers and there has been variability in results from different research centers, perhaps due to technical factors. Here, we sought to optimize technical parameters for CSF miRNA studies. We examined different RNA isolation methods and performed miRNA expression profiling with TaqMan® miRNA Arrays. More specifically, we developed a customized …

Low Arousal Positive Emotional Stimuli Attenuate Aberrant Working Memory Processing In Persons With Mild Cognitive Impairment, Lucas S. Broster, Shonna L. Jenkins, Sarah D. Holmes, Gregory A. Jicha, Yang Jiang

Behavioral Science Faculty Publications

Emotional enhancement effects on memory have been reported to mitigate the pathophysiology of Alzheimer’s disease (AD). However, relative to their manifestation in persons without pathologic aging, these effects may be reduced in magnitude or even deleterious, especially in tasks that more closely model ecologic memory performance. Based upon a synthesis of such reports, we hypothesized that in persons with AD low arousal positive stimuli would evoke relatively intact emotional enhancement effects, but that high arousal negative stimuli would evoke disordered emotional enhancement effects. To assess this, participants with and without mild cognitive impairment (MCI) presumed to be due to AD …

Dynamic Range Of Frontoparietal Functional Modulation Is Associated With Working Memory Capacity Limitations In Older Adults, Jonathan G. Hakun, Nathan F. Johnson

Physical Therapy Faculty Publications

Older adults tend to over-activate regions throughout frontoparietal cortices and exhibit a reduced range of functional modulation during WM task performance compared to younger adults. While recent evidence suggests that reduced functional modulation is associated with poorer task performance, it remains unclear whether reduced range of modulation is indicative of general WM capacity-limitations. In the current study, we examined whether the range of functional modulation observed over multiple levels of WM task difficulty (N-Back) predicts in-scanner task performance and out-of-scanner psychometric estimates of WM capacity. Within our sample (60–77 years of age), age was negatively associated with frontoparietal modulation range. …

Chronic Traumatic Encephalopathy-Integration Of Canonical Traumatic Brain Injury Secondary Injury Mechanisms With Tau Pathology, Jacqueline R. Kulbe, Edward D. Hall

Spinal Cord and Brain Injury Research Center Faculty Publications

In recent years, a new neurodegenerative tauopathy labeled Chronic Traumatic Encephalopathy (CTE), has been identified that is believed to be primarily a sequela of repeated mild traumatic brain injury (TBI), often referred to as concussion, that occurs in athletes participating in contact sports (e.g. boxing, football, football, rugby, soccer, ice hockey) or in military combatants, especially after blast-induced injuries. Since the identification of CTE, and its neuropathological finding of deposits of hyperphosphorylated tau protein, mechanistic attention has been on lumping the disorder together with various other non-traumatic neurodegenerative tauopathies. Indeed, brains from suspected CTE cases that have come to autopsy …

Single-Base Resolution Mapping Of 5-Hydroxymethylcytosine Modifications In Hippocampus Of Alzheimer's Disease Subjects, Elizabeth M. Ellison, Melissa A. Bradley-Whitman, Mark A. Lovell

Chemistry Faculty Publications

Epigenetic modifications to cytosine have been shown to regulate transcription in cancer, embryonic development, and recently neurodegeneration. While cytosine methylation studies are now common in neurodegenerative research, hydroxymethylation studies are rare, particularly genome-wide mapping studies. As an initial study to analyze 5-hydroxymethylcytosine (5-hmC) in the Alzheimer’s disease (AD) genome, reduced representation hydroxymethylation profiling (RRHP) was used to analyze more than 2 million sites of possible modification in hippocampal DNA of sporadic AD and normal control subjects. Genes with differentially hydroxymethylated regions were filtered based on previously published microarray data for altered gene expression in hippocampal DNA of AD subjects. Our …

Targeting Mitochondrial Dysfunction In Cns Injury Using Methylene Blue; Still A Magic Bullet?, Hemendra J. Vekaria, Lora Talley Watts, Ai-Ling Lin, Patrick G. Sullivan

Spinal Cord and Brain Injury Research Center Faculty Publications

Complex, multi-factorial secondary injury cascades are initiated following traumatic brain injury, which makes this a difficult disease to treat. The secondary injury cascades following the primary mechanical tissue damage, are likely where effective therapeutic interventions may be targeted. One promising therapeutic target following brain injury are mitochondria. Mitochondria are complex organelles found within the cell, which act as powerhouses within all cells by supplying ATP. These organelles are also necessary for calcium cycling, redox signaling and play a major role in the initiation of cell death pathways. When mitochondria become dysfunctional, there is a tendency for the cell to loose …

Clinically Silent Alzheimer's And Vascular Pathologies Influence Brain Networks Supporting Executive Function In Healthy Older Adults, Brian T. Gold, Christopher A. Brown, Jonathan G. Hakun, Leslie M. Shaw, John Q. Trojanowski, Charles D. Smith

Neuroscience Faculty Publications

Aging is associated with declines in executive function. We examined how executive functional brain systems are influenced by clinically silent Alzheimer’s disease (AD) pathology and cerebral white matter hyperintensities (WMHs). Twenty-nine younger adults and thirty-four cognitively normal older adults completed a working memory paradigm while functional magnetic resonance imaging (fMRI) was performed. Older adults further underwent lumbar cerebrospinal fluid (CSF) draw for assessment of AD pathology and FLAIR imaging for assessment of WMHs. Accurate working memory performance in both age groups was associated with high fronto-visual functional connectivity (fC). However, in older adults, higher expression of fronto-visual fC was linked …

Systems Biology Approach To Late-Onset Alzheimer's Disease Genome-Wide Association Study Identifies Novel Candidate Genes Validated Using Brain Expression Data And Caenorhabditis Elegans Experiments, Shubhabrata Mukherjee, Joshua C. Russell, Daniel T. Carr, Jeremy D. Burgess, Mariet Allen, Daniel J. Serie, Kevin L. Boehme, John S. K. Kauwe, Adam C. Naj, David W. Fardo, Dennis W. Dickson, Thomas J. Montine, Nilufer Ertekin-Taner, Matt R. Kaeberlein, Paul K. Crane

Biostatistics Faculty Publications

Introduction—We sought to determine whether a systems biology approach may identify novel late-onset Alzheimer's disease (LOAD) loci.

Methods—We performed gene-wide association analyses and integrated results with human protein-protein interaction data using network analyses. We performed functional validation on novel genes using a transgenic Caenorhabditis elegans Aβ proteotoxicity model and evaluated novel genes using brain expression data from people with LOAD and other neurodegenerative conditions.

Results—We identified 13 novel candidate LOAD genes outside chromosome 19. Of those, RNA interference knockdowns of the C. elegans orthologs of UBC, NDUFS3, EGR1, and ATP5H were associated with Aβ …

Thiamine Deficiency And Neurodegeneration: The Interplay Among Oxidative Stress, Endoplasmic Reticulum Stress, And Autophagy, Dexiang Liu, Zunji Ke, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Thiamine (vitamin B1) is an essential nutrient and indispensable for normal growth and development of the organism due to its multilateral participation in key biochemical and physiological processes. Humans must obtain thiamine from their diet since it is synthesized only in bacteria, fungi, and plants. Thiamine deficiency (TD) can result from inadequate intake, increased requirement, excessive deletion, and chronic alcohol consumption. TD affects multiple organ systems, including the cardiovascular, muscular, gastrointestinal, and central and peripheral nervous systems. In the brain, TD causes a cascade of events including mild impairment of oxidative metabolism, neuroinflammation, and neurodegeneration, which are commonly observed in …

Challenges And Considerations Related To Studying Dementia In Blacks/African Americans, Eseosa T. Ighodaro, Peter T. Nelson, Walter A. Kukull, Frederick A. Schmitt, Erin L. Abner, Allison M. Caban-Holt, Shoshana H. Bardach, Derrick C. Hord, Crystal M. Glover, Gregory A. Jicha, Linda J. Van Eldik, Alexander X. Byrd, Anita Fernander

Neuroscience Faculty Publications

Blacks/African Americans have been reported to be ~2–4 times more likely to develop clinical Alzheimer’s disease (AD) compared to Whites. Unfortunately, study design challenges (e.g., recruitment bias), racism, mistrust of healthcare providers and biomedical researchers, confounders related to socioeconomic status, and other sources of bias are often ignored when interpreting differences in human subjects categorized by race. Failure to account for these factors can lead to misinterpretation of results, reification of race as biology, discrimination, and missed or delayed diagnoses. Here we provide a selected historical background, discuss challenges, present opportunities, and suggest considerations for studying health outcomes among racial/ethnic …

Interleukin-6 (Il-6) Rs1800796 And Cyclin Dependent Kinase Inhibitor (Cdkn2a/Cdkn2b) Rs2383207 Are Associated With Ischemic Stroke In Indigenous West African Men, Rufus Akinyemi, Donna K. Arnett, Hemant K. Tiwari, Bruce Ovbiagele, Fred Sarfo, Vinodh Srinivasasainagendra, Marguerite Ryan Irvin, Abiodun Adeoye, Rodney T. Perry, Albert Akpalu, Carolyn Jenkins, Lukman Owolabi, Reginald Obiako, Kolawole Wahab, Emmanuel Sanya, Morenikeji Komolafe, Michael Fawale, Philip Adebayo, Godwin Osaigbovo, Taofiki Sunmonu, Paul Olowoyo, Innocent Chukwuonye, Yahaya Obiabo, Onoja Akpa, Sylvia Melikam, Raelle Saulson, Raj Kalaria, Adesola Ogunniyi, Mayowa Owolabi

Epidemiology and Environmental Health Faculty Publications

Background—Inherited genetic variations offer a possible explanation for the observed peculiarities of stroke in sub – Saharan African populations. Interleukin–6 polymorphisms have been previously associated with ischemic stroke in some non-African populations.

Aim—Herein we investigated, for the first time, the association of genetic polymorphisms of IL-6 and CDKN2A- CDKN2B and other genes with ischemic stroke among indigenous West African participants in the Stroke Investigative Research and Education Network (SIREN) Study.

Methods—Twenty-three previously identified single nucleotide polymorphisms (SNPs) in 14 genes of relevance to the neurobiology of ischemic stroke were investigated. Logistic regression models adjusting for known …

Impulsive Personality Dimensions Are Associated With Altered Behavioral Performance And Neural Responses In The Monetary Incentive Delay Task, Ruolei Gu, Yang Jiang, Seth Kiser, Chelsea L. Black, Lucas S. Broster, Yue-Jia Luo, Thomas H. Kelly

Behavioral Science Faculty Publications

Individual differences in dimensions of impulsivity personality including disinhibition and sensation seeking modulate approach responses to reinforcing stimuli, such as drugs and money. The current study examined the effects of monetary incentive on both behavioral performance and electrophysiological activity among individuals varying in disinhibition and sensation seeking. The monetary incentive delay (MID) task was completed under electroencephalogram (EEG) recording. Behavioral data showed that higher disinhibition and sensation-seeking were associated with lower performance accuracy. Event-related potential (ERP) data showed that high reinforcement cues elicited a larger late positive component (LPC) than other conditions among high disinhibition participants, indicating its strong emotional …

Identification Of Changes In Neuronal Function As A Consequence Of Aging And Tauopathic Neurodegeneration Using A Novel And Sensitive Magnetic Resonance Imaging Approach, Sarah N. Fontaine, Alexandria Ingram, Ryan A. Cloyd, Shelby E. Meier, Emily Miller, Danielle N. Lyons, Grant K. Nation, Elizabeth Mechas, Blaine Weiss, Chiara Lanzillotta, Fabio Di Domenico, Frederick A. Schmitt, David K. Powell, Moriel H. Vandsburger, Jose Francisco Abisambra

Sanders-Brown Center on Aging Faculty Publications

Tauopathies, the most common of which is Alzheimer’s disease (AD), constitute the most crippling neurodegenerative threat to our aging population. Tauopathic patients have significant cognitive decline accompanied by irreversible and severe brain atrophy, and it is thought that neuronal dysfunction begins years before diagnosis. Our current understanding of tauopathies has yielded promising therapeutic interventions but have all failed in clinical trials. This is partly due to the inability to identify and intervene in an effective therapeutic window early in the disease process. A major challenge that contributes to the definition of an early therapeutic window is limited technologies. To address …

Down Syndrome: Age-Dependence Of Pib Binding In Postmortem Frontal Cortex Across The Lifespan, Harry Levine Iii, H. Peter Spielmann, Sergey V. Matveev, Francesca Macchiavello Cauvi, M. Paul Murphy, Tina L. Beckett, Katie Mccarty, Ira T. Lott, Eric Doran, Frederick A. Schmitt, Elizabeth Head

Sanders-Brown Center on Aging Faculty Publications

Beta-amyloid (Aβ) deposition in brain accumulates as a function of age in people with Down syndrome (DS) with subsequent development into Alzheimer disease neuropathology, typically by 40 years of age. In vivo imaging using the Pittsburgh Compound B (PiB) ligand has facilitated studies linking Aβ, cognition, and dementia in DS. However, there are no studies of PiB binding across the lifespan in DS. The current study describes in vitro ³H-PiB binding in the frontal cortex of autopsy cases with DS compared to non-DS controls. Tissue from 64 cases included controls (N=25) and DS (N=39). In DS, ³H-PiB binding …

Functional Human Grin2b Promoter Polymorphism And Variation Of Mental Processing Speed In Older Adults, Yang Jiang, Ming Kuan Lin, Gregory A. Jicha, Xiuhua Ding, Sabrina L. Mcilwrath, David W. Fardo, Lucas S. Broster, Frederick A. Schmitt, Richard J. Kryscio, Robert H. Lipsky

Behavioral Science Faculty Publications

We investigated the role of a single nucleotide polymorphism rs3764030 (G > A) within the human GRIN2B promoter in mental processing speed in healthy, cognitively intact, older adults. In vitro DNA-binding and reporter gene assays of different allele combinations in transfected cells showed that the A allele was a gain-of-function variant associated with increasing GRIN2B mRNA levels. We tested the hypothesis that individuals with A allele will have better memory performance (i.e. faster reaction times) in older age. Twenty-eight older adults (ages 65-86) from a well-characterized longitudinal cohort were recruited and performed a modified delayed match-to-sample task. The rs3764030 polymorphism was …