Medicine and Health Sciences Commons^™

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 …

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 …

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 …

Brain Microvascular Injury And White Matter Disease Provoked By Diabetes-Associated Hyperamylinemia, Han Ly, Nirmal Verma, Fengen Wu, Miao Liu, Kathryn E. Saatman, Peter T. Nelson, John T. Slevin, Larry B. Goldstein, Geert Jan Biessels, Florin Despa

Pharmacology and Nutritional Sciences Faculty Publications

OBJECTIVE: The brain blood vessels of patients with type 2 diabetes and dementia have deposition of amylin, an amyloidogenic hormone cosecreted with insulin. It is not known whether vascular amylin deposition is a consequence or a trigger of vascular injury. We tested the hypothesis that the vascular amylin deposits cause endothelial dysfunction and microvascular injury and are modulated by amylin transport in the brain via plasma apolipoproteins.

METHODS: Rats overexpressing amyloidogenic (human) amylin in the pancreas (HIP rats) and amylin knockout (AKO) rats intravenously infused with aggregated amylin were used for in vivo phenotyping. We also carried out biochemical analyses …

Prevalence And Prognostic Features Of Ecg Abnormalities In Acute Stroke: Findings From The Siren Study Among Africans, Abiodun M. Adeoye, Okechukwu S. Ogah, Bruce Ovbiagele, Rufus Akinyemi, Vincent Shidali, Francis Agyekum, Akinyemi Aje, Oladimeji Adebayo, Joshua O. Akinyemi, Philip Kolo, Lambert Tetteh Appiah, Henry Iheonye, Uwanuruochi Kelechukwu, Amusa Ganiyu, Taiwo O. Olunuga, Onoja Akpa, Ojo Olakanmi Olagoke, Fred Stephen Sarfo, Kolawole Wahab, Samuel Olowookere, Adekunle Fakunle, Albert Akpalu, Philip B. Adebayo, Kwadwo Nkromah, Joseph Yaria, Philip Ibinaiye, Godwin Ogbole, Aridegbe Olumayowa, Sulaiman Lakoh, Benedict Calys-Tagoe, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Background

Africa has a growing burden of stroke with associated high morbidity and a 3-year fatality rate of 84%. Cardiac disease contributes to stroke occurrence and outcomes, but the precise relationship of abnormalities as noted on a cheap and widely available test, the electrocardiogram (ECG), and acute stroke outcomes have not been previously characterized in Africans.

Objectives

The study assessed the prevalence and prognoses of various ECG abnormalities among African acute stroke patients encountered in a multisite, cross-national epidemiologic study.

Methods

We included 890 patients from Nigeria and Ghana with acute stroke who had 12-lead ECG recording within first 24 …

Risk Of Incident Clinical Diagnosis Of Alzheimer's Disease-Type Dementia Attributable To Pathology-Confirmed Vascular Disease, Hiroko H. Dodge, Jian Zhu, Randy Woltjer, Peter T. Nelson, David A. Bennett, Nigel J. Cairns, David W. Fardo, Jeffrey A. Kaye, Deniz-Erten Lyons, Nora Mattek, Julie A. Schneider, Lisa C. Silbert, Chengjie Xiong, Lei Yu, Frederick A. Schmitt, Richard J. Kryscio, Erin L. Abner, Smart Data Consortium

Sanders-Brown Center on Aging Faculty Publications

INTRODUCTION: The presence of cerebrovascular pathology may increase the risk of clinical diagnosis of Alzheimer's disease (AD).

METHODS: We examined excess risk of incident clinical diagnosis of AD (probable and possible AD) posed by the presence of lacunes and large infarcts beyond AD pathology using data from the Statistical Modeling of Aging and Risk of Transition study, a consortium of longitudinal cohort studies with more than 2000 autopsies. We created six mutually exclusive pathology patterns combining three levels of AD pathology (low, moderate, or high AD pathology) and two levels of vascular pathology (without lacunes and large infarcts or with …

Widespread Tau Seeding Activity At Early Braak Stages, Jennifer L. Furman, Jaime Vaquer-Alicea, Charles L. White, Nigel J. Cairns, Peter T. Nelson, Marc I. Diamond

Pathology and Laboratory Medicine Faculty Publications

Transcellular propagation of tau aggregates may underlie the progression of pathology in Alzheimer's disease (AD) and other tauopathies. Braak staging (B1, B2, B3) is based on phospho-tau accumulation within connected brain regions: entorhinal cortex (B1); hippocampus/limbic system (B2); and frontal and parietal lobes (B3). We previously developed a specific and sensitive assay that uses flow cytometry to quantify tissue seeding activity based on fluorescence resonance energy transfer (FRET) in cells that stably express tau reporter proteins. In a tauopathy mouse model, we have detected seeding activity far in advance of histopathological changes. It remains unknown whether individuals with AD also …