Medicine and Health Sciences Commons^™

Post-Acquisition Processing Confounds In Brain Volumetric Quantification Of White Matter Hyperintensities, Ahmed A. Bahrani, Omar M. Al-Janabi, Erin L. Abner, Shoshana H. Bardach, Richard J. Kryscio, Donna M. Wilcock, Charles D. Smith, Gregory A. Jicha

Neurology Faculty Publications

BACKGROUND: Disparate research sites using identical or near-identical magnetic resonance imaging (MRI) acquisition techniques often produce results that demonstrate significant variability regarding volumetric quantification of white matter hyperintensities (WMH) in the aging population. The sources of such variability have not previously been fully explored.

NEW METHOD: 3D FLAIR sequences from a group of randomly selected aged subjects were analyzed to identify sources-of-variability in post-acquisition processing that can be problematic when comparing WMH volumetric data across disparate sites. The methods developed focused on standardizing post-acquisition protocol processing methods to develop a protocol with less than 0.5% inter-rater variance.

RESULTS: A series …

Co-Prescription Network Reveals Social Dynamics Of Opioid Doctor Shopping, Brea L. Perry, Kai Cheng Yang, Patrick Kaminski, Meltem Odabas, Jaehyuk Park, Michelle M. Martel, Carrie B. Oser, Patricia R. Freeman, Yong-Yeol Ahn, Jeffery C. Talbert

Psychology Faculty Publications

This paper examines network prominence in a co-prescription network as an indicator of opioid doctor shopping (i.e., fraudulent solicitation of opioids from multiple prescribers). Using longitudinal data from a large commercially insured population, we construct a network where a tie between patients is weighted by the number of shared opioid prescribers. Given prior research suggesting that doctor shopping may be a social process, we hypothesize that active doctor shoppers will occupy central structural positions in this network. We show that network prominence, operationalized using PageRank, is associated with more opioid prescriptions, higher predicted risk for dangerous morphine dosage, opioid overdose, …

Neural Mechanisms Of The Rejection-Aggression Link, David S. Chester, Donald R. Lynam, Richard Milich, C. Nathan Dewall

Psychology Faculty Publications

Social rejection is a painful event that often increases aggression. However, the neural mechanisms of this rejection–aggression link remain unclear. A potential clue may be that rejected people often recruit the ventrolateral prefrontal cortex’s (VLPFC) self-regulatory processes to manage the pain of rejection. Using functional MRI, we replicated previous links between rejection and activity in the brain’s mentalizing network, social pain network and VLPFC. VLPFC recruitment during rejection was associated with greater activity in the brain’s reward network (i.e. the ventral striatum) when individuals were given an opportunity to retaliate. This retaliation-related striatal response was associated with greater levels of …

A Longitudinal Analysis Of The Impact Of Child Custody Loss On Drug Use And Crime Among A Sample Of African American Mothers, Kathi L. H. Harp, Carrie B. Oser

Health Management and Policy Faculty Publications

This study examines the influence of child custody loss on drug use and crime among a sample of African American mothers. Two types of custody loss are examined: informal custody loss (child living apart from mother but courts not involved), and official loss (child removed from mother’s care by authorities).

Methods—Using data from 339 African American women, longitudinal random coefficient models analyzed the effects of each type of custody loss on subsequent drug use and crime.

Results—Results indicated that both informal and official custody loss predicted increased drug use, and informal loss predicted increased criminal involvement. Findings demonstrate …

Pathway Of Protection: Ethnic Identity, Self-Esteem, And Substance Use Among Multiracial Youth, Sycarah Fisher, Tamika C. B. Zapolski, Chelsea Sheehan, Jessica Barnes-Najor

Educational, School, and Counseling Psychology Faculty Publications

Fifty percent of adolescents have tried an illicit drug and 70% have tried alcohol by the end of high school, with even higher rates among multiracial youth. Ethnic identity is a protective factor against substance use for minority groups. However, little is known about the mechanisms that facilitate its protective effects, and even less is known about this relationship for multiracial youth. The purpose of the present study was to examine the protective effect of ethnic identity on substance use and to determine whether this relationship operated indirectly through self-esteem, a strong predictor of substance use for among adolescent populations. …

Examining The Protective Effect Of Ethnic Identity On Drug Attitudes And Use Among A Diverse Youth Population, Tamika C. B. Zapolski, Sycarah Fisher, Devin E. Banks, Devon J. Hensel, Jessica Barnes-Najor

Educational, School, and Counseling Psychology Faculty Publications

Ethnic identity is an important buffer against drug use among minority youth. However, limited work has examined pathways through which ethnic identity mitigates risk. School-aged youth (N = 34,708; 52 % female) of diverse backgrounds (i.e., African American (n = 5333), Asian (n = 392), Hispanic (n = 662), Multiracial (n = 2129), Native American (n = 474), and White (n = 25718) in grades 4–12 provided data on ethnic identity, drug attitudes, and drug use. After controlling for gender and grade, higher ethnic identity was associated with lower past month drug use …

Impact Of Home Visit Capacity On Genetic Association Studies Of Late-Onset Alzheimer's Disease, David W. Fardo, Laura E. Gibbons, Shubhabrata Mukherjee, M. Maria Glymour, Wayne Mccormick, Susan M. Mccurry, James D. Bowen, Eric B. Larson, Paul K. Crane

Biostatistics Faculty Publications

INTRODUCTION—Findings for genetic correlates of late-onset Alzheimer's disease (LOAD) in studies that rely solely on clinic visits may differ from those with capacity to follow participants unable to attend clinic visits.

METHODS—We evaluated previously identified LOAD-risk single nucleotide variants in the prospective Adult Changes in Thought study, comparing hazard ratios (HRs) estimated using the full data set of both in-home and clinic visits (n = 1697) to HRs estimated using only data that were obtained from clinic visits (n = 1308). Models were adjusted for age, sex, principal components to account for ancestry, and additional health indicators.

RESULTS …

Csf Protein Changes Associated With Hippocampal Sclerosis Risk Gene Variants Highlight Impact Of Grn/Pgrn, David W. Fardo, Yuriko Katsumata, John S. K. Kauwe, Yuetiva Deming, Oscar Harari, Carlos Cruchaga, Alzheimer’S Disease Neuroimaging Initiative, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

Objective—Hippocampal sclerosis of aging (HS-Aging) is a common cause of dementia in older adults. We tested the variability in cerebrospinal fluid (CSF) proteins associated with previously identified HS-Aging risk single nucleotide polymorphisms (SNPs).

Methods—Alzheimer’s Disease Neuroimaging Initiative cohort (ADNI; n=237) data, combining both multiplexed proteomics CSF and genotype data, were used to assess the association between CSF analytes and risk SNPs in four genes (SNPs): GRN (rs5848), TMEM106B (rs1990622), ABCC9 (rs704180), and KCNMB2 (rs9637454). For controls, non-HS-Aging SNPs in APOE (rs429358/rs7412) and MAPT (rs8070723) were also analyzed against Aβ1-42 and total tau CSF analytes.

Results—The GRN risk …

Mental Health Treatment Seeking Patterns And Preferences Of Appalachian Women With Depression, Claire Snell-Rood, Emily Hauenstein, Carl G. Leukefeld, Frances Feltner, Amber Marcum, Nancy E. Schoenberg

Behavioral Science Faculty Publications

This qualitative study explored social-cultural factors that shape treatment seeking behaviors among depressed rural, low-income women in Appalachia—a region with high rates of depression and a shortage of mental health services. Recent research shows that increasingly rural women are receiving some form of treatment and identifying their symptoms as depression. Using purposive sampling, investigators recruited 28 depressed low-income women living in Appalachian Kentucky and conducted semistructured interviews on participants’ perceptions of depression and treatment seeking. Even in this sample of women with diverse treatment behaviors (half reported current treatment), participants expressed ambivalence about treatment and its potential to promote recovery. …

Intimate Partner Violence And Women's Cancer Quality Of Life, Ann L. Coker, Diane R. Follingstad, Lisandra S. Garcia, Heather M. Bush

CRVAW Faculty Journal Articles

Purpose

Because intimate partner violence (IPV) may disproportionately impact women’s quality of life (QOL) when undergoing cancer treatment, women experiencing IPV were hypothesized to have (a) more symptoms of depression or stress and (b) lower QOL as measured with the Functional Assessment of Cancer Therapy (FACT-B) and Functional Assessment of Chronic Illness Therapy—Spiritual Well-being (FACIT-SP) Scales relative to those never experiencing IPV.

Methods

Women, aged 18–79, who were included in one of two state cancer registries from 2009 to 2015 with a recent incident, primary, invasive biopsy-confirmed cancer diagnosis were recruited and asked to complete a phone interview, within 12 …

Partner Influence In Diet And Exercise Behaviors: Testing Behavior Modeling, Social Control, And Normative Body Size, Brea Perry, Gabriele Ciciurkaite, Christy Freadreacea Brady, Justin Garcia

Sociology Faculty Publications

Previous research has documented social contagion in obesity and related health behaviors, but less is known about the social processes underlying these patterns. Focusing on married or cohabitating couples, we simultaneously explore three potential social mechanisms influencing obesity: normative body size, social control, and behavior modeling. We analyze the association between partner characteristics and the obesity-related health behaviors of focal respondents, comparing the effects of partners’ body type, partners’ attempts to manage respondents’ eating behaviors, and partners’ own health behaviors on respondents’ health behaviors (physical activity, fruit and vegetable consumption, and fast food consumption). Data on 215 partners are extracted …

Dna Methylation Signatures Of Chronic Low-Grade Inflammation Are Associated With Complex Diseases, Symen Ligthart, Carola Marzi, Stella Aslibekyan, Michael M. Mendelson, Karen N. Conneely, Toshiko Tanaka, Elena Colicino, Lindsay L. Waite, Roby Joehanes, Weihua Guan, Jennifer A. Brody, Cathy Elks, Riccardo Marioni, Min A. Jhun, Golareh Agha, Jan Bressler, Cavin K. Ward-Caviness, Brian H. Chen, Tianxiao Huan, Kelly Bakulski, Elias L. Salfati, Whi-Empc Investigators, Giovanni Fiorito, Charge Epigenetics Of Coronary Heart Disease, Simone Wahl, Katharina Schramm, Jin Sha, Dena G. Hernandez, Allan C. Just, Jennifer A. Smith, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Background: Chronic low-grade inflammation reflects a subclinical immune response implicated in the pathogenesis of complex diseases. Identifying genetic loci where DNA methylation is associated with chronic low-grade inflammation may reveal novel pathways or therapeutic targets for inflammation.

Results: We performed a meta-analysis of epigenome-wide association studies (EWAS) of serum C-reactive protein (CRP), which is a sensitive marker of low-grade inflammation, in a large European population (n = 8863) and trans-ethnic replication in African Americans (n = 4111). We found differential methylation at 218 CpG sites to be associated with CRP (P < 1.15 × 10^–7) in the discovery panel …

Accuracy Of Name And Age Data Provided About Network Members In A Social Network Study Of People Who Use Drugs: Implications For Constructing Sociometric Networks, April M. Young, Abby E. Rudolph, Amanda E. Su, Lee King, Susan Jent, Jennifer R. Havens

Epidemiology and Environmental Health Faculty Publications

Purpose—Network analysis has become increasingly popular in epidemiologic research, but the accuracy of data key to constructing risk networks is largely unknown. Using network data from people who use drugs (PWUD), the study examined how accurately PWUD reported their network members’ (i.e., alters’) names and ages.

Methods—Data were collected from 2008 to 2010 from 503 PWUD residing in rural Appalachia. Network ties (n=897) involved recent (past 6 months) sex, drug co-usage, and/or social support. Participants provided alters’ names, ages, and relationship-level characteristics; these data were cross-referenced to that of other participants to identify participant-participant relationships and to determine …

Reduced Efficacy Of Anti-AΒ Immunotherapy In A Mouse Model Of Amyloid Deposition And Vascular Cognitive Impairment Comorbidity, Erica M. Weekman, Tiffany L. Sudduth, Carly N. Caverly, Timothy J. Kopper, Oliver W. Phillips, David K. Powell, Donna M. Wilcock

Sanders-Brown Center on Aging Faculty Publications

Vascular cognitive impairment and dementia (VCID) is the second most common form of dementia behind Alzheimer's disease (AD). It is estimated that 40% of AD patients also have some form of VCID. One promising therapeutic for AD is anti-Aβ immunotherapy, which uses antibodies against Aβ to clear it from the brain. While successful in clearing Aβ and improving cognition in mice, anti-Aβ immunotherapy failed to reach primary cognitive outcomes in several different clinical trials. We hypothesized that one potential reason the anti-Aβ immunotherapy clinical trials were unsuccessful was due to this high percentage of VCID …

African American Female Offender's Use Of Alternative And Traditional Health Services After Re-Entry: Examining The Behavioral Model For Vulnerable Populations, Carrie B. Oser, Amanda M. Bunting, Erin L. Pullen, Danelle Stevens-Watkins

Sociology Faculty Publications

This is the first known study to use the Gelberg-Andersen Behavioral Model for Vulnerable Populations to predict African American women's use of three types of health services (alternative, hospitalization, and ambulatory) in the 18 months after release from prison. In the multivariate models, the most robust predictors of all three types of service utilization were in the vulnerable theoretical domains. Alternative health services were predicted by ethnic community membership, higher religiosity, and HIV/HCV. Hospitalizations were predicted by the lack of barriers to health care and disability. Ambulatory office visits were predicted by more experiences of gendered racism, a greater number …

Similarities And Differences In Sexual Risk Behaviors Between Young Black Msm Who Do And Do Not Have Sex With Females, Richard A. Crosby, Leandro Mena, Angelica Geter, Demarc Hickson

Health, Behavior & Society Faculty Publications

The objective of this study is to determine whether young Black MSM who also have sex with females report similar levels of sexual risk behaviors as those not having sex with females. YBMSM (N = 400) were recruited from an STI clinic, located in the Southern U.S. Men completed an audio-computer assisted self-interview and donated specimens for STI/HIV testing. Forty-three percent recently engaged in penile-vaginal sex. They were less likely to report having concurrent partners (P = .01), unprotected fellatio (P = .04), multiple partners as a bottom (P < .02), any unprotected anal sex as a bottom (P < .013), and any anal sex (P = .007). They were equally likely …

Colorectal Cancer Prevention: Perspectives Of Key Players From Social Networks In A Low-Income Rural Us Region, Nancy E. Schoenberg, Kathryn Eddens, Adam Jonas, Claire Snell-Rood, Christina R. Studts, Benjamin Broder-Oldach, Mira L. Katz

Behavioral Science Faculty Publications

Social networks influence health behavior and health status. Within social networks, “key players” often influence those around them, particularly in traditionally underserved areas like the Appalachian region in the USA. From a total sample of 787 Appalachian residents, we identified and interviewed 10 key players in complex networks, asking them what comprises a key player, their role in their network and community, and ideas to overcome and increase colorectal cancer (CRC) screening. Key players emphasized their communication skills, resourcefulness, and special occupational and educational status in the community. Barriers to CRC screening included negative perceptions of the colonoscopy screening procedure, …

Altered Lysosomal Proteins In Neural-Derived Plasma Exosomes In Preclinical Alzheimer Disease, Edward J. Goetzl, Adam Boxer, Janice B. Schwartz, Erin L. Abner, Ronald C. Petersen, Bruce L. Miller, Dimitrios Kapogiannis

Sanders-Brown Center on Aging Faculty Publications

OBJECTIVE: Diverse autolysosomal proteins were quantified in neurally derived blood exosomes from patients with Alzheimer disease (AD) and controls to investigate disordered neuronal autophagy.

METHODS: Blood exosomes obtained once from patients with AD (n = 26) or frontotemporal dementia (n = 16), other patients with AD (n = 20) both when cognitively normal and 1 to 10 years later when diagnosed, and case controls were enriched for neural sources by anti-human L1CAM antibody immunoabsorption. Extracted exosomal proteins were quantified by ELISAs and normalized with the CD81 exosomal marker.

RESULTS: Mean exosomal levels of cathepsin D, lysosome-associated membrane …

Closed Head Injury In An Age-Related Alzheimer Mouse Model Leads To An Altered Neuroinflammatory Response And Persistent Cognitive Impairment, Scott J. Webster, Linda J. Van Eldik, D. Martin Watterson, Adam D. Bachstetter

Sanders-Brown Center on Aging Faculty Publications

Epidemiological studies have associated increased risk of Alzheimer's disease (AD)-related clinical symptoms with a medical history of head injury. Currently, little is known about pathophysiology mechanisms linked to this association. Persistent neuroinflammation is one outcome observed in patients after a single head injury. Neuroinflammation is also present early in relevant brain regions during AD pathology progression. In addition, previous mechanistic studies in animal models link neuroinflammation as a contributor to neuropathology and cognitive impairment in traumatic brain injury (TBI) or AD-related models. Therefore, we explored the potential interplay of neuroinflammatory responses in TBI and AD by analysis of the temporal …

Unlocking The Mysteries Of Tdp-43, Keith A. Josephs, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

No abstract provided.

Sugihara Causality Analysis Of Scalp Eeg For Detection Of Early Alzheimer's Disease, Joseph C. Mcbride, Xiaopeng Zhao, Nancy B. Munro, Greg A. Jicha, Frederick A. Schmitt, Richard J. Kryscio, Charles D. Smith, Yang Jiang

Sanders-Brown Center on Aging Faculty Publications

Recently, Sugihara proposed an innovative causality concept, which, in contrast to statistical predictability in Granger sense, characterizes underlying deterministic causation of the system. This work exploits Sugihara causality analysis to develop novel EEG biomarkers for discriminating normal aging from mild cognitive impairment (MCI) and early Alzheimer's disease (AD). The hypothesis of this work is that scalp EEG based causality measurements have different distributions for different cognitive groups and hence the causality measurements can be used to distinguish between NC, MCI, and AD participants. The current results are based on 30-channel resting EEG records from 48 age-matched participants (mean age 75.7 …

Self-Reported Memory Complaints: Implications From A Longitudinal Cohort With Autopsies, Richard J. Kryscio, Erin L. Abner, Gregory E. Cooper, David W. Fardo, Greg A. Jicha, Peter T. Nelson, Charles D. Smith, Linda J. Van Eldik, Lijie Wan, Frederick A. Schmitt

Sanders-Brown Center on Aging Faculty Publications

OBJECTIVE: We assessed salience of subjective memory complaints (SMCs) by older individuals as a predictor of subsequent cognitive impairment while accounting for risk factors and eventual neuropathologies.

METHODS: Subjects (n = 531) enrolled while cognitively intact at the University of Kentucky were asked annually if they perceived changes in memory since their last visit. A multistate model estimated when transition to impairment occurred while adjusting for intervening death. Risk factors affecting the timing and probability of an impairment were identified. The association between SMCs and Alzheimer-type neuropathology was assessed from autopsies (n = 243).

RESULTS: SMCs were …

Chess Improves Cancer Caregivers' Burden And Mood: Results Of An Ehealth Rct, Lori L. Dubenske, David H. Gustafson, Kang Namkoong, Robert P. Hawkins, Amy K. Atwood, Roger L. Brown, Ming-Yuan Chih, Fiona Mctavish, Cindy L. Carmack, Mary K. Buss, Ramaswamy Govindan, James F. Cleary

Community & Leadership Development Faculty Publications

OBJECTIVE: Informal caregivers (family and friends) of people with cancer are often unprepared for their caregiving role, leading to increased burden or distress. Comprehensive Health Enhancement Support System (CHESS) is a Web-based lung cancer information, communication, and coaching system for caregivers. This randomized trial reports the impact on caregiver burden, disruptiveness, and mood of providing caregivers access to CHESS versus the Internet with a list of recommended lung cancer websites.

METHODS: A total of 285 informal caregivers of patients with advanced nonsmall cell lung cancer were randomly assigned to a comparison group that received Internet or a treatment group that …

Sexual Coercion And Sexual Violence At First Intercourse Associated With Sexually Transmitted Infections, Corrine M. Williams, Emily R. Clear, Ann L. Coker

CRVAW Faculty Journal Articles

BACKGROUND: Violence against women has been associated with subsequent risky sexual behaviors and sexually transmitted infections (STIs). We explored whether sexual coercion or violence at first intercourse was associated with self-reported STIs.

METHODS: Using nationally representative data from the 2006 to 2010 National Survey of Family Growth, we analyzed female respondents aged 18 to 44 (n = 9466) who answered questions on coercion at first intercourse (wantedness, voluntariness, and types of force used) and STIs using logistic regression analyses. We explored degrees of coercion, which we label as neither, sexual coercion (unwanted or nonphysical force), or sexual violence (involuntary or …

Intracranial Injection Of Gammagard, A Human Ivig, Modulates The Inflammatory Response Of The Brain And Lowers AΒ In App/Ps1 Mice Along A Different Time Course Than Anti-AΒ Antibodies, Tiffany L. Sudduth, Abigail Greenstein, Donna M. Wilcock

Sanders-Brown Center on Aging Faculty Publications

Gammagard IVIg is a therapeutic approach to treat Alzheimer's disease currently in phase 3 clinical trials. Despite the reported efficacy of the approach the mechanism of action is poorly understood. We have previously shown that intracranial injection of anti-Aβ antibodies into the frontal cortex and hippocampus reveals important information regarding the time course of events once the agent is in the brain. In the current study we compared IVIg, mouse-pooled IgG, and the anti-Aβ antibody 6E10 injected intracranially into the frontal cortex and hippocampus of 7-month-old APP/PS1 mice. We established a time course of events ranging from 1 …

Transforming The Healthcare Response To Intimate Partner Violence And Taking Best Practices To Scale, Michele R. Decker, Shannon Frattaroli, Brigid Mccaw, Ann L. Coker, Elizabeth Miller, Phyllis Sharps, Wendy G. Lane, Mahua Mandal, Kelli Hirsch, Donna M. Strobino, Wendy L. Bennett, Jacquelyn Campbell, Andrea Gielen

CRVAW Faculty Journal Articles

BACKGROUND: Intimate partner violence (IPV) is prevalent among adolescent and adult women, with significant physical, sexual, and mental health consequences. In 2011, the Institute of Medicine's Clinical Preventive Services for Women consensus report recommended universal screening for violence as a component of women's preventive services; this policy has been adopted by the Health Resources and Services Administration (HRSA). These policy developments require that effective clinic-based interventions be identified, easily implemented, and taken to scale.

METHODS: To foster dialogue about implementing effective interventions, we convened a symposium entitled "Responding to Violence Against Women: Emerging Evidence, Implementation Science, and Innovative Interventions," on …

Conformational Altered P53 As An Early Marker Of Oxidative Stress In Alzheimer's Disease, Laura Buizza, Giovanna Cenini, Cristina Lanni, Giulia Ferrari-Toninelli, Chiara Prandelli, Stefano Govoni, Erica Buoso, Marco Racchi, Maria Barcikowska, Maria Styczynska, Aleksandra Szybinska, D. Allan Butterfield, Maurizio Memo, Daniela Uberti

Sanders-Brown Center on Aging Faculty Publications

In order to study oxidative stress in peripheral cells of Alzheimer's disease (AD) patients, immortalized lymphocytes derived from two peculiar cohorts of patients, referring to early onset AD (EOSAD) and subjects harboured AD related mutation (ADmut), were used. Oxidative stress was evaluated measuring i) the typical oxidative markers, such as HNE Michel adducts, 3 Nitro-Tyrosine residues and protein carbonyl on protein extracts, ii) and the antioxidant capacity, following the enzymatic kinetic of superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GRD). We found that the signs of oxidative stress, measured as oxidative marker levels, were evident only in ADmut …

Elevated Stearoyl-Coa Desaturase In Brains Of Patients With Alzheimer's Disease, Giuseppe Astarita, Kwang-Mook Jung, Vitaly Vasilevko, Nicholas V. Dipatrizio, Sarah K. Martin, David H. Cribbs, Elizabeth Head, Carl W. Cotman, Daniele Piomelli

Sanders-Brown Center on Aging Faculty Publications

The molecular bases of Alzheimer's disease (AD) remain unclear. We used a lipidomic approach to identify lipid abnormalities in the brains of subjects with AD (N = 37) compared to age-matched controls (N = 17). The analyses revealed statistically detectable elevations in levels of non-esterified monounsaturated fatty acids (MUFAs) and mead acid (20:3n-9) in mid-frontal cortex, temporal cortex and hippocampus of AD patients. Further studies showed that brain mRNAs encoding for isoforms of the rate-limiting enzyme in MUFAs biosynthesis, stearoyl-CoA desaturase (SCD-1, SCD-5a and SCD-5b), were elevated in subjects with AD. The monounsaturated/saturated fatty acid ratio ('desaturation index')--displayed a strong …

Epigenetic Silencing Of Nucleolar Rrna Genes In Alzheimer's Disease, Maciej Pietrzak, Grzegorz Rempala, Peter T. Nelson, Jing-Juan Zheng, Michal Hetman

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Ribosomal deficits are documented in mild cognitive impairment (MCI), which often represents an early stage Alzheimer's disease (AD), as well as in advanced AD. The nucleolar rRNA genes (rDNA), transcription of which is critical for ribosomal biogenesis, are regulated by epigenetic silencing including promoter CpG methylation.

METHODOLOGY/PRINCIPAL FINDINGS: To assess whether CpG methylation of the rDNA promoter was dysregulated across the AD spectrum, we analyzed brain samples from 10 MCI-, 23 AD-, and, 24 age-matched control individuals using bisulfite mapping. The rDNA promoter became hypermethylated in cerebro-cortical samples from MCI and AD groups. In parietal cortex, the rDNA promoter …

Microglial P38Α Mapk Is A Key Regulator Of Proinflammatory Cytokine Up-Regulation Induced By Toll-Like Receptor (Tlr) Ligands Or Beta-Amyloid (Aβ), Adam D. Bachstetter, Bin Xing, Lucia De Almeida, Edgardo R. Dimayuga, D. Martin Watterson, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Overproduction of proinflammatory cytokines from activated microglia has been implicated as an important contributor to pathophysiology progression in both acute and chronic neurodegenerative diseases. Therefore, it is critical to elucidate intracellular signaling pathways that are significant contributors to cytokine overproduction in microglia exposed to specific stressors, especially pathways amenable to drug interventions. The serine/threonine protein kinase p38α MAPK is a key enzyme in the parallel and convergent intracellular signaling pathways involved in stressor-induced production of IL-1β and TNFα in peripheral tissues, and is a drug development target for peripheral inflammatory diseases. However, much less is known about the quantitative …