Medicine and Health Sciences Commons^™

Pairwise Correlation Analysis Of The Alzheimer’S Disease Neuroimaging Initiative (Adni) Dataset Reveals Significant Feature Correlation, Erik D. Huckvale, Matthew W. Hodgman, Brianna B. Greenwood, Devorah O. Stucki, Katrisa M. Ward, Mark T. W. Ebbert, John S. K. Kauwe, The Alzheimer’S Disease Neuroimaging Initiative, The Alzheimer’S Disease Metabolomics Consortium, Justin B. Miller

Sanders-Brown Center on Aging Faculty Publications

The Alzheimer’s Disease Neuroimaging Initiative (ADNI) contains extensive patient measurements (e.g., magnetic resonance imaging [MRI], biometrics, RNA expression, etc.) from Alzheimer’s disease (AD) cases and controls that have recently been used by machine learning algorithms to evaluate AD onset and progression. While using a variety of biomarkers is essential to AD research, highly correlated input features can significantly decrease machine learning model generalizability and performance. Additionally, redundant features unnecessarily increase computational time and resources necessary to train predictive models. Therefore, we used 49,288 biomarkers and 793,600 extracted MRI features to assess feature correlation within the ADNI dataset to determine the …

Editorial: Roles Of Sleep Disruption And Circadian Rhythm Alterations On Neurodegeneration And Alzheimer's Disease, Marilyn J. Duncan, Sigrid C. Veasey, Phyllis Zee

Neuroscience Faculty Publications

No abstract provided.

White Matter Hyperintensity Volume And Location: Associations With Wm Microstructure, Brain Iron, And Cerebral Perfusion, Christopher E. Bauer, Valentinos Zachariou, Elayna R. Seago, Brian T. Gold

Neuroscience Faculty Publications

Cerebral white matter hyperintensities (WMHs) represent macrostructural brain damage associated with various etiologies. However, the relative contributions of various etiologies to WMH volume, as assessed via different neuroimaging measures, is not well-understood. Here, we explored associations between three potential early markers of white matter hyperintensity volume. Specifically, the unique variance in total and regional WMH volumes accounted for by white matter microstructure, brain iron concentration and cerebral blood flow (CBF) was assessed. Regional volumes explored were periventricular and deep regions. Eighty healthy older adults (ages 60–86) were scanned at 3 Tesla MRI using fluid-attenuated inversion recovery, diffusion tensor imaging (DTI), …

Healthy Dietary Intake Moderates The Effects Of Age On Brain Iron Concentration And Working Memory Performance, Valentinos Zachariou, Christopher E. Bauer, Elayna R. Seago, Georgia Panayiotou, Edward D. Hall, D. Allan Butterfield, Brian T. Gold

Neuroscience Faculty Publications

Age-related brain iron accumulation is linked with oxidative stress, neurodegeneration and cognitive decline. Certain nutrients can reduce brain iron concentration in animal models, however, this association is not well established in humans. Moreover, it remains unknown if nutrition can moderate the effects of age on brain iron concentration and/or cognition. Here, we explored these issues in a sample of 73 healthy older adults (61-86 years old), while controlling for several factors such as age, gender, years of education, physical fitness and alcohol-intake. Quantitative susceptibility mapping was used for assessment of brain iron concentration and participants performed an N-Back paradigm to …

Inflammatory Regulation Of Cns Barriers After Traumatic Brain Injury: A Tale Directed By Interleukin-1, Colleen N. Bodnar, James B. Watson, Emma K. Higgins, Ning Quan, Adam D. Bachstetter

Neuroscience Faculty Publications

Several barriers separate the central nervous system (CNS) from the rest of the body. These barriers are essential for regulating the movement of fluid, ions, molecules, and immune cells into and out of the brain parenchyma. Each CNS barrier is unique and highly dynamic. Endothelial cells, epithelial cells, pericytes, astrocytes, and other cellular constituents each have intricate functions that are essential to sustain the brain’s health. Along with damaging neurons, a traumatic brain injury (TBI) also directly insults the CNS barrier-forming cells. Disruption to the barriers first occurs by physical damage to the cells, called the primary injury. Subsequently, during …

The Effects Of Myelin On Macrophage Activation Are Phenotypic Specific Via Cpla2 In The Context Of Spinal Cord Injury Inflammation, Timothy J. Kopper, Bei Zhang, William M. Bailey, Kara E. Bethel, John C. Gensel

Physiology Faculty Publications

Spinal cord injury (SCI) produces chronic, pro-inflammatory macrophage activation that impairs recovery. The mechanisms driving this chronic inflammation are not well understood. Here, we detail the effects of myelin debris on macrophage physiology and demonstrate a novel, activation state-dependent role for cytosolic phospholipase-A2 (cPLA₂) in myelin-mediated potentiation of pro-inflammatory macrophage activation. We hypothesized that cPLA₂ and myelin debris are key mediators of persistent pro-inflammatory macrophage responses after SCI. To test this, we examined spinal cord tissue 28-days after thoracic contusion SCI in 3-month-old female mice and observed both cPLA₂ activation and intracellular accumulation of lipid-rich myelin …

Regional N-Glycan And Lipid Analysis From Tissues Using Maldi-Mass Spectrometry Imaging, Alexandra E. Stanback, Lindsey R. Conroy, Lyndsay E. A. Young, Tara R. Hawkinson, Kia H. Markussen, Harrison A. Clarke, Derek B. Allison, Ramon C. Sun

Neuroscience Faculty Publications

N-glycans and lipids are structural metabolites that play important roles in cellular processes. Both show unique regional distribution in tissues; therefore, spatial analyses of these metabolites are crucial to our understanding of cellular physiology. Matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) is an innovative technique that enables in situ detection of analytes with spatial distribution. This workflow details a MALDI-MSI protocol for the spatial profiling of N-glycans and lipids from tissues following application of enzyme and MALDI matrix.

For complete details on the use and execution of this protocol, please refer to Drake et al. (2018) and Andres et al. (2020).

Cloning And Functional Characterizations Of Circular Rnas From The Human Mapt Locus, Justin R. Welden

Theses and Dissertations--Molecular and Cellular Biochemistry

Under pathophysiological conditions, the microtubule protein tau (MAPT) forms neurofibrillary tangles that are the hallmark of sporadic Alzheimer’s disease as well as familial frontotemporal dementias linked to chromosome 17 (FTDP-17). In this work, I report that MAPT forms circular RNAs through backsplicing of exon 12 to either exon 10 or exon 7 (12→10; 12→7), and that these circular RNAs are translated into proteins.

Using stable cell lines overexpressing the circular tau RNAs 12→7 and 12→10, we have discovered that the tau circular RNA 12→7 is translated in a rolling circle, giving rise to multiple proteins. This circular RNA …

Cognitive Abilities In Hearing Loss: Perceived And Performance Abilities Of Adults Related To Attention, Memory, And Social Cognition, Karah Gottschalk

Theses and Dissertations--Gerontology

Hearing loss is the most common sensory deficit noted in aging adults. It is commonly known to reduce an individual’s ability to detect, identify, and localize sounds and speech and to cause issues in communication. However, there are other less commonly discussed impacts that hearing loss has beyond the auditory system. Literature suggests a correlation between hearing loss and cognition in aging adults. Similar to hearing loss, the domains of cognition experience performance and functional changes across the life span. In an aging adult, changes related to cognition are also suggested to be associated with hearing loss. This study aimed …