Nervous System Diseases Commons^™

Biomarkers For Managing Neurodegenerative Diseases, Lara Cheslow, Adam E. Snook, Scott A. Waldman

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Neurological disorders are the leading cause of cognitive and physical disability worldwide, affecting 15% of the global population. Due to the demographics of aging, the prevalence of neurological disorders, including neurodegenerative diseases, will double over the next two decades. Unfortunately, while available therapies provide symptomatic relief for cognitive and motor impairment, there is an urgent unmet need to develop disease-modifying therapies that slow the rate of pathological progression. In that context, biomarkers could identify at-risk and prodromal patients, monitor disease progression, track responses to therapy, and parse the causality of molecular events to identify novel targets for further clinical investigation. …

Digital Clock Drawing As An Alzheimer's Disease Susceptibility Biomarker: Associations With Genetic Risk Score And Apoe In Older Adults, L I Thompson, M Cummings, S Emrani, David J. Libon, A Ang, C Karjadi, R Au, C Liu

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

BACKGROUND: Alzheimer's disease (AD) is the leading cause of dementia in older adults, but most people are not diagnosed until significant neuronal loss has likely occurred along with a decline in cognition. Non-invasive and cost-effective digital biomarkers for AD have the potential to improve early detection.

OBJECTIVE: We examined the validity of DCTclockTM (a digitized clock drawing task) as an AD susceptibility biomarker.

DESIGN: We used two primary independent variables, Apolipoprotein E (APOE) ε4 allele carrier status and polygenic risk score (PRS). We examined APOE and PRS associations with DCTclockTM composite scores as dependent measures.

SETTING: We used existing data …

Exploring Drivers Of Sex-Based Disparities In Relapsing Multiple Sclerosis, Stephanie K. Buxhoeveden

Theses and Dissertations

Females are three times more susceptible to relapsing multiple sclerosis (MS) and males typically have more severe disease, but the molecular underpinnings of these sex-based disease disparities are unknown and represent a critical knowledge gap.Subject Population: Blood samples from a demographically homogenous group of treatment naïve males and females with relapsing-MS and healthy controls. Research Design: Cross-sectional combinatorial omics pilot study. Instruments: Whole transcriptomic analysis with messenger RNA (mRNA) expression profiling using next generation sequencing (RNA-seq) and micro-RNA (miRNA) expression using NanoString technology. Aim 1) Identify and compare the actively expressed mRNAs in the transcriptome of males and …

Developing An Assay For Easy And Rapid Detection Of Als Biomarker(S): A Hypothesis, Swati Dhasmana, Anupam Dhasmana, Meena Jaggi, Murali M. Yallapu, Subhash C. Chauhan

Research Symposium

Background: Death of motor neurons is the key pathology underlying neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). Biomarkers are chemical changes in the biological fluids. Biomarkers serving as a diagnostic tool should be specific to the concerned disease. Biomarkers indicating disease progression should be very sensitive to demonstrate changes during the disease process as well as therapeutics development. Biomarkers proposed for ALS include poly (GP) repeats in C9orf72, neurofilaments, miRNAs, glutathione and 4HNE in CSF, SOD1/TDP43 protein, poly (GP) repeats in C9orf72, neurofilaments, T regulatory cells, CRP, chitotriosidase, creatinine, creatinine kinase, miRNAs, glutamate, albumin, uric acid, glutathione, ferritin, …

Alzheimer’S Disease Studies In The Tex-Mex Border: Dissecting A Complex Multifactorial Problem, Ney Alliey-Rodriguez, Rosa V. Pirela, Alvaro Diaz-Badillo, Karla Lopez Lorenzo, Noe Garza, Frank Gilliam, Eron G. Manusov, Gladys E. Maestre

Research Symposium

Purpose: Alzheimer’s Disease (ALZ) is the leading cause of dementia in the aging population, and Latinos have >3 times higher risk to develop dementia than the overall US population. Although several studies have examined for possible causes of this increased risk, lack of comprehensive information plus a reduced number of Latino samples available in each study have hindered the answers.

Description: The University of Texas Rio Grande Valley has joined two large studies looking for multiple biomarkers associated with ALZ: The South Texas Alzheimer’s Center Clinical Data Repository and Biobank (STAC) and the Texas Alzheimer’s Research and Care Consortium (TARCC). …

Identifying Voice-Based Digital Biomarkers Of Parkinson's Disease, Rachelle Beshay, Madison Gill, Michael Shiraishi, Rahul Soangra

Student Scholar Symposium Abstracts and Posters

Introduction: Parkinson's disease is a disorder in the central nervous system that causes tremors, abnormal gait and balance, and muscle rigidity due to loss of function in parts of the brain. Traditionally, Parkinson's is identified by the physical symptoms seen in a patient's gait and motor skills, but irregular speech patterns (hypokinetic dysarthria) is one of the first symptoms to be derived from the disease. Objective: The goal of this ongoing study is to use Mel Frequency Centrum Coefficients (MFCC), to diagnose Parkinson's in the early stages by identifying hypokinetic dysarthria. MFCC's process speech recognition patterns and produce …

Novel Biomarkers Of Ciliary Extracellular Vesicles Interact With Ciliopathy And Alzheimer’S Associated Proteins, Ashraf M. Mohieldin, Amal Alachkar, John R. Yates Iii, Surya M. Nauli

Pharmacy Faculty Articles and Research

Ciliary extracellular vesicles (ciEVs), released from primary cilia, contain functional proteins that play an important role in cilia structure and functions. We have recently shown that ciEVs and cytosolic extracellular vesicles (cyEVs) have unique and distinct biomarkers. While ciEV biomarkers have shown some interactions with known ciliary proteins, little is known about the interaction of ciEV proteins with proteins involved in ciliopathy and neurodegenerative disorders. Here, we reveal for the first time the protein-protein interaction (PPI) between the top five ciEVs biomarkers with ciliopathy and Alzheimer disease (AD) proteins. These results support the growing evidence of the critical physiological roles …

Pre-Clinical Advancements In Biomarkers, Tools, And Therapeutics For A Metabolic Neurodegenerative Disease, Zoë Simmons

Theses and Dissertations--Molecular and Cellular Biochemistry

Glycogen is the storage form of glucose and a highly important substrate for cellular metabolism. Characterization of the enzymes and mechanisms of glycogen metabolism began over 70 years ago and over the last 20 years, a previously unknown protein called laforin has emerged as an important contributor to glycogen metabolism homeostasis. Multiple labs demonstrated that laforin is a glycogen phosphatase and mutations in the gene encoding laforin cause the formation of aberrant glycogen-like aggregates called Lafora bodies (LBs). LBs are cytoplasmic, water-insoluble aggregates that drive neurodegeneration and early death in Lafora disease (LD) patients. The direct relationship between mutated laforin, …

Core Alzheimer’S Disease Cerebrospinal Fluid Biomarker Assays Are Not Affected By Aspiration Or Gravity Drip Extraction Methods, James D. Doecke, Cindy Francois, Christopher J. Fowler, Erik Stoops, Pierrick Bourgeat, Stephanie R. Rainey-Smith, Qiao-Xin Li, Colin L. Masters, Ralph N. Martins, Victor L. Villemagne, Steven J. Collins, Hugo Marcel Vanderstichele

Research outputs 2014 to 2021

Background: CSF biomarkers are well-established for routine clinical use, yet a paucity of comparative assessment exists regarding CSF extraction methods during lumbar puncture. Here, we compare in detail biomarker profiles in CSF extracted using either gravity drip or aspiration. Methods: Biomarkers for β-amyloidopathy (Aβ1–42, Aβ1–40), tauopathy (total tau), or synapse pathology (BACE1, Neurogranin Trunc-p75, α-synuclein) were assessed between gravity or aspiration extraction methods in a sub-population of the Australian Imaging, Biomarkers and Lifestyle (AIBL) study (cognitively normal, N = 36; mild cognitive impairment, N = 8; Alzheimer’s disease, N = 6). Results: High biomarker concordance between extraction methods was seen …

Word-List Intrusion Errors Predict Progression To Mild Cognitive Impairment, Kelsey R Thomas, Joel Eppig, Emily C Edmonds, Diane M Jacobs, David J Libon, Rhoda Au, David P Salmon, Mark W Bondi, Alzheimer’S Disease Neuroimaging Initiative

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

OBJECTIVE: Preclinical Alzheimer's disease (AD) defined by a positive AD biomarker in the presence of normal cognition is presumed to precede mild cognitive impairment (MCI). Subtle cognitive deficits and cognitive inefficiencies in preclinical AD may be detected through process and error scores on neuropsychological tests in those at risk for progression to MCI.

METHOD: Cognitively normal participants (n = 525) from the Alzheimer's Disease Neuroimaging Initiative were followed for up to 5 years and classified as either stable normal (n = 305) or progressed to MCI (n = 220). Cox regressions were used to determine whether baseline process scores on …

Autoantibodies As Diagnostic Biomarkers For The Detection And Subtyping Of Multiple Sclerosis, Cassandra Demarshall, Eric Goldwaser, Abhirup Sarkar, George Godsey, Nimish Acharya, Umashanger Thayasivam, Benjamin Belinka, Robert Nagele

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

The goal of this preliminary proof-of-concept study was to use human protein microarrays to identify blood-based autoantibody biomarkers capable of diagnosing multiple sclerosis (MS). Using sera from 112 subjects, including 51 MS subjects, autoantibody biomarkers effectively differentiated MS subjects from age- and gender-matched normal and breast cancer controls with 95.0% and 100% overall accuracy, but not from subjects with Parkinson's disease. Autoantibody biomarkers were also useful in distinguishing subjects with the relapsing-remitting form of MS from those with the secondary progressive subtype. These results demonstrate that autoantibodies can be used as noninvasive blood-based biomarkers for the detection and subtyping of …

Utility And Origin Of Blood-Based Autoantibodies For Early Detection And Diagnosis Of Neurodegenerative Diseases, Cassandra Demarshall

Graduate School of Biomedical Sciences Theses and Dissertations

Autoantibodies are self-reactive antibodies that have been widely implicated as causal agents of autoimmune diseases. They are found in the blood of all human sera, regardless of age, gender, or the presence or absence of disease. While the underlying reason for their ubiquity remains unknown, it has been hypothesized that they participate in the clearance of blood-borne cell and tissue debris generated in both healthy and diseased individuals on a daily basis. Although much evidence supports this debris clearance role, recent studies also suggest a causal role for autoantibodies in disease. My thesis work has focused on this "cause and/or …