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Information Theoretic Measures For Quantifying Sequence-Ensemble Relationships Of Intrinsically Disordered Proteins, Megan C Cohan, Kiersten M Ruff, Rohit V Pappu

2010-2019 OA Pubs

Intrinsically disordered proteins (IDPs) contribute to a multitude of functions. De novo design of IDPs should open the door to modulating functions and phenotypes controlled by these systems. Recent design efforts have focused on compositional biases and specific sequence patterns as the design features. Analysis of the impact of these designs on sequence-function relationships indicates that individual sequence/compositional parameters are insufficient for describing sequence-function relationships in IDPs. To remedy this problem, we have developed information theoretic measures for sequence-ensemble relationships (SERs) of IDPs. These measures rely on prior availability of statistically robust conformational ensembles derived from all atom simulations. We …

Comparing Sensitivity To Change Using The 6-Item Versus The 17-Item Hamilton Depression Rating Scale In The Guided Randomized Controlled Trial, Boadie W Dunlop, Sagar V Parikh, Anthony J Rothschild, Michael E Thase, Charles Debattista, Charles R Conway, Brent P Forester, Francis M Mondimore, Richard C Shelton, Matthew Macaluso, Jennifer Logan, Paul Traxler, James Li, Holly Johnson, John F Greden

Open Access Publications

BACKGROUND: Previous research suggests that the 17-item Hamilton Depression Rating Scale (HAM-D17) is less sensitive in detecting differences between active treatment and placebo for major depressive disorder (MDD) than is the HAM-D6 scale, which focuses on six core depression symptoms. Whether HAM-D6 shows greater sensitivity when comparing two active MDD treatment arms is unknown.

METHODS: This post hoc analysis used data from the intent-to-treat (ITT) cohort (N = 1541) of the Genomics Used to Improve DEpression Decisions (GUIDED) trial, a rater- and patient-blinded randomized controlled trial. GUIDED compared combinatorial pharmacogenomics-guided care with treatment as usual (TAU) in patients with MDD. …

Safety Of Paclitaxel-Coated Balloon Angioplasty For Femoropopliteal Peripheral Artery Disease, Kenneth Ouriel, Mark A. Adelman, Kenneth Rosenfield, Dierk Scheinert, Marianne Brodmann, Constantino Peña, Patrick Geraghty, Arthur Lee, Roseann White, Daniel G. Clair

2010-2019 OA Pubs

OBJECTIVES: The aim of this study was to assess safety outcomes of femoropopliteal drug-coated balloon (DCB) angioplasty using patient-level data from the Lutonix clinical program.

BACKGROUND: A recent systematic review and meta-analysis of heterogenous trials and summary-level data identified increased long-term mortality in patients treated with paclitaxel-coated balloons and stents.

METHODS: We evaluated DCB angioplasty (n = 1,093) and uncoated balloon angioplasty (percutaneous transluminal angioplasty [PTA]) (n = 250) outcomes in LEVANT 1 (The Lutonix Paclitaxel-Coated Balloon for the Prevention of Femoropopliteal Restenosis), LEVANT 2 (Moxy Drug Coated Balloon vs. Standard Balloon Angioplasty for the Treatment of Femoropopliteal Arteries), and …

Multicenter Clinical Evaluation Of Etest Meropenem-Vaborbactam (Biomérieux) For Susceptibility Testing Of Enterobacterales (Enterobacteriaceae) And Pseudomonas Aeruginosa, Sophonie Jean, Sheri Garrett, Claire Anglade, Laurence Bridon, Leanne Davies, Omai B Garner, Jennifer Richards, Meghan Wallace, Mandy Wootton, Carey-Ann D. Burnham

Open Access Publications

Meropenem-vaborbactam (MEV) is a novel carbapenem-beta-lactamase inhibitor combination antibiotic approved by the U.S. Food and Drug Administration (FDA) for treatment of complicated urinary tract infections, including pyelonephritis, in adults. In this study, we evaluated the performance of Etest MEV (bioMérieux, Marcy l'Etoile, France) compared to that of broth microdilution for 629

A Qualitative Study Of Older Adults' Perspectives On Initiating Exercise And Mindfulness Practice, Diana C Parra, Julie Loebach Wetherell, Alexandria Van Zandt, Ross C Brownson, Janardan Abhishek, Eric J Lenze

Open Access Publications

BACKGROUND: Mindfulness practice and exercise are ways by which older adults can improve and maintain their physical, emotional and cognitive health.

METHODS: This single-site qualitative study gathered insights of older adults' perceptions about initiating and maintaining mindfulness and exercise practices. We carried out focus groups with 41 adults aged 65-85 who had recently initiated Mindfulness Based Stress Reduction (MBSR), structured exercise, or their combination as part of participation in a clinical trial. We used a semi-structured interview to ask them open-ended questions regarding the benefits, barriers and facilitators of participating in mindfulness and/or exercise interventions. The interview also included questions …

Immunomodulatory Activity Of Humanized Anti-Il-7r Monoclonal Antibody Rn168 In Subjects With Type 1 Diabetes, Kevan C Herold, Jing Hughes, Janet B Mcgill, Et Al

Open Access Publications

BACKGROUND: The cytokine IL-7 is critical for T cell development and function. We performed a Phase Ib study in patients with type 1 diabetes (T1D) to evaluate how blockade of IL-7 would affect immune cells and relevant clinical responses.

METHODS: Thirty-seven subjects with T1D received s.c. RN168, a monoclonal antibody that blocks the IL -7 receptor α (IL7Rα) in a dose-escalating study.

RESULTS: Between 90% and 100% IL-7R occupancy and near-complete inhibition of pSTAT5 was observed at doses of RN168 1 mg/kg every other week (Q2wk) and greater. There was a significant decline in CD4+ and CD8+ effector and central …

Humanized Zebrafish Enhance Human Hematopoietic Stem Cell Survival And Promote Acute Myeloid Leukemia Clonal Diversity, Vinothkumar Rajan, Nicole Melong, Wing Hing Wong, Benjamin King, R. Spencer Tong, Nithin Mahajan, Daniel Gaston, Troy Lund, David Rittenberg, Graham Dellaire, Clinton J. V. Campbell, Todd Druley, Jason N. Berman

Open Access Publications

Xenograft models are invaluable tools in establishing the current paradigms of hematopoiesis and leukemogenesis. The zebrafish has emerged as a robust alternative xenograft model but, like mice, lack specific cytokines that mimic the microenvironment found in human patients. To address this critical gap, we generated the first humanized zebrafish that express human hematopoietic-specific cytokines (GM-CSF, SCF, and SDF1α). Termed GSS fish, these zebrafish promote survival, self-renewal and multilineage differentiation of human hematopoietic stem and progenitor cells and result in enhanced proliferation and hematopoietic niche-specific homing of primary human leukemia cells. Using error-corrected RNA sequencing, we determined that patient-derived leukemias transplanted …

Comparison Of Reproducibility, Accuracy, Sensitivity, And Specificity Of Mirna Quantification Platforms, Paula M Godoy, Andrea J Barczak, Peter Dehoff, Srimeenakshi Srinivasan, Alton Etheridge, David Galas, Saumya Das, David J Erle, Louise C Laurent

Open Access Publications

Given the increasing interest in their use as disease biomarkers, the establishment of reproducible, accurate, sensitive, and specific platforms for microRNA (miRNA) quantification in biofluids is of high priority. We compare four platforms for these characteristics: small RNA sequencing (RNA-seq), FirePlex, EdgeSeq, and nCounter. For a pool of synthetic miRNAs, coefficients of variation for technical replicates are lower for EdgeSeq (6.9%) and RNA-seq (8.2%) than for FirePlex (22.4%); nCounter replicates are not performed. Receiver operating characteristic analysis for distinguishing present versus absent miRNAs shows small RNA-seq (area under curve 0.99) is superior to EdgeSeq (0.97), nCounter (0.94), and FirePlex (0.81). …

The Aminoalkylindole Bml-190 Negatively Regulates Chitosan Synthesis Via The Cyclic Amp/Protein Kinase A1 Pathway In Cryptococcus Neoformans, Brian T Maybruck, Woei C Lam, Charles A Specht, Ma Xenia G Ilagan, Maureen J Donlin, Jennifer K Lodge

Open Access Publications

No abstract provided.

Adaptation Of The Clinical Dementia Rating Scale For Adults With Down Syndrome, Christina N Lessov-Schlaggar, Olga L Del Rosario, John C Morris, Beau M Ances, Bradley L Schlaggar, John N Constantino

Open Access Publications

BACKGROUND: Adults with Down syndrome (DS) are at increased risk for Alzheimer disease dementia, and there is a pressing need for the development of assessment instruments that differentiate chronic cognitive impairment, acute neuropsychiatric symptomatology, and dementia in this population of patients.

METHODS: We adapted a widely used instrument, the Clinical Dementia Rating (CDR) Scale, which is a component of the Uniform Data Set used by all federally funded Alzheimer Disease Centers for use in adults with DS, and tested the instrument among 34 DS patients recruited from the community. The participants were assessed using two versions of the modified CDR-a …

The Role Of Glia In Epilepsy, Intellectual Disability, And Other Neurodevelopmental Disorders In Tuberous Sclerosis Complex, Michael Wong

Open Access Publications

BACKGROUND: Tuberous sclerosis complex (TSC) is a genetic disorder characterized by severe neurological manifestations, including epilepsy, intellectual disability, autism, and a range of other behavioral and psychiatric symptoms, collectively referred to as TSC-associated neuropsychiatric disorders (TAND). Various tumors and hamartomas affecting different organs are the pathological hallmarks of the disease, especially cortical tubers of the brain, but specific cellular and molecular abnormalities, such as involving the mechanistic target of rapamycin (mTOR) pathway, have been identified that also cause or contribute to neurological manifestations of TSC independent of gross structural lesions. In particular, while neurons are immediate mediators of neurological symptoms, …

Clearance Of Chikungunya Virus Infection In Lymphoid Tissues Is Promoted By Treatment With An Agonistic Anti-Cd137 Antibody, Jun P Hong, Mary K Mccarthy, Bennett J Davenport, Thomas E Morrison, Michael S Diamond

Open Access Publications

CD137, a member of the tumor necrosis factor receptor superfamily of cell surface proteins, acts as a costimulatory receptor on T cells, natural killer cells, B cell subsets, and some dendritic cells. Agonistic anti-CD137 monoclonal antibody (MAb) therapy has been combined with other chemotherapeutic agents in human cancer trials. Based on its ability to promote tumor clearance, we hypothesized that anti-CD137 MAb might activate immune responses and resolve chronic viral infections. We evaluated anti-CD137 MAb therapy in a mouse infection model of chikungunya virus (CHIKV), an alphavirus that causes chronic polyarthritis in humans and is associated with reservoirs of CHIKV …

Regional Gene Repression By Dna Double-Strand Breaks In G1 Phase Cells, Caitlin E. Purman, Patrick L. Collins, Sofia I. Porter, Ankita Saini, Harshath Gupta, Barry P. Sleckman, Eugene M. Oltz

Open Access Publications

DNA damage responses (DDR) to double-strand breaks (DSBs) alter cellular transcription programs at the genome-wide level. Through processes that are less well understood, DSBs also alter transcriptional responses locally, which may be important for efficient DSB repair. Here, we developed an approach to elucidate the

Cytogps: A Web-Enabled Karyotype Analysis Tool For Cytogenetics, Zachary B Abrams, Lin Zhang, Lynne V Abruzzo, Nyla A Heerema, Suli Li, Tom Dillon, Ricky Rodriguez, Kevin R Coombes, Philip R O Payne

Open Access Publications

SUMMARY: Karyotype data are the most common form of genetic data that is regularly used clinically. They are collected as part of the standard of care in many diseases, particularly in pediatric and cancer medicine contexts. Karyotypes are represented in a unique text-based format, with a syntax defined by the International System for human Cytogenetic Nomenclature (ISCN). While human-readable, ISCN is not intrinsically machine-readable. This limitation has prevented the full use of complex karyotype data in discovery science use cases. To enhance the utility and value of karyotype data, we developed a tool named CytoGPS. CytoGPS first parses ISCN karyotypes …

Eric Stephanson Oral History.

Pediatric Palliative Care Oral History Project

Mr. Eric Stephanson begins the interview by describing his path into ministry and divinity and how that intersected over a lifetime, into a career in pediatric palliative and pediatric hospice care. Mr. Stephanson describes how spiritual guidance grew into the services offered at Canuck Place Children's Hospice, the first free-standing North American children's hospice, and how Mr. Stephanson took a chance opportunity to be on the first cohort of multidisciplinary professionals working to deliver palliative services to children in North America. Mr. Stephanson then goes on to describe how his life experience as a minister helped prepare him to be …

Gantenerumab Reduces Amyloid-Β Plaques In Patients With Prodromal To Moderate Alzheimer's Disease: A Pet Substudy Interim Analysis, Gregory Klein, Paul Delmar, Nicola Voyle, Sunita Rehal, Carsten Hofmann, Danielle Abi-Saab, Mirjana Andjelkovic, Smiljana Ristic, Guoqiao Wang, Randall Bateman, Geoffrey A Kerchner, Monika Baudler, Paulo Fontoura, Rachelle Doody

Open Access Publications

BACKGROUND: We previously investigated low doses (105 or 225 mg) of gantenerumab, a fully human monoclonal antibody that binds and removes aggregated amyloid-β by Fc receptor-mediated phagocytosis, in the SCarlet RoAD (SR) and Marguerite RoAD (MR) phase 3 trials. Several lines of evidence suggested that higher doses may be necessary to achieve clinical efficacy. We therefore designed a positron emission tomography (PET) substudy to evaluate the effect of gantenerumab uptitrated to 1200 mg every 4 weeks on amyloid-β plaques as measured using florbetapir PET in patients with prodromal to moderate Alzheimer's disease (AD).

METHODS: A subset of patients enrolled in …

Distinct Roles Of Interferon Alpha And Beta In Controlling Chikungunya Virus Replication And Modulating Neutrophil-Mediated Inflammation, Lindsey E Cook, Marissa C Locke, Alissa R Young, Kristen Monte, Matthew L Hedberg, Raeann M Shimak, Kathleen C F Sheehan, Deborah J Veis, Michael S Diamond, Deborah J Lenschow

Open Access Publications

Type I interferons (IFNs) are key mediators of the innate immune response. Although members of this family of cytokines signal through a single shared receptor, biochemical and functional variation exists in response to different IFN subtypes. While previous work has demonstrated that type I IFNs are essential to control infection by chikungunya virus (CHIKV), a globally emerging alphavirus, the contributions of individual IFN subtypes remain undefined. To address this question, we evaluated CHIKV pathogenesis in mice lacking IFN-β (IFN-β knockout [IFN-β-KO] mice or mice treated with an IFN-β-blocking antibody) or IFN-α (IFN regulatory factor 7 knockout [IRF7-KO] mice or mice …

Dosimetric Feasibility Of Utilizing The Viewray Magnetic Resonance Guided Linac System For Image-Guided Spine Stereotactic Body Radiation Therapy, Gage Redler, Tynan Stevens, Jochen Cammin, Martha Malin, Olga Green, Sasa Mutic, Sean Pitroda, Bulent Aydogan

Open Access Publications

INTRODUCTION: Spine stereotactic body radiation therapy (SBRT) achieves favorable outcomes compared to conventional radiotherapy doses/fractionation. The spinal cord is the principal dose-limiting organ-at-risk (OAR), and safe treatment requires precise immobilization/localization. Therefore, image guidance is paramount to successful spine SBRT. Conventional X-ray imaging and alignment to surrogate bony anatomy may be inadequate, whereas magnetic resonance imaging (MRI) directly visualizes the dose-limiting cord. This work assessed the dosimetric capability of the ViewRay (ViewRay Inc. Oakwood Village, OH) magnetic resonance (MR) guided linac (MR-Linac) for spine SBRT.

METHODS: Eight spine SBRT patients without orthopedic hardware who were previously treated on a TrueBeam using …

Stacy Remke Oral History.

Pediatric Palliative Care Oral History Project

Ms. Stacy Remke begins the interview by describing her initial career path in social work around aging and how she came to develop her interest in care planning for pediatric end of life needs. Ms. Remke then describes her observation that both providers and parents would not have meaningful discussions about the realities and practicalities of children who were seriously ill or dying. She also noticed that providers were resistant to utilizing hospice services for seriously ill pediatric patients and that they expressed sentiments like "you'll take care of my patients over my dead body." Ms. Remke then describes the …

Let-7 Micrornas Regulate Microglial Function And Suppress Glioma Growth Through Toll-Like Receptor 7, Alice Buonfiglioli, David H Gutmann, Et Al

Open Access Publications

Microglia express Toll-like receptors (TLRs) that sense pathogen- and host-derived factors, including single-stranded RNA. In the brain, let-7 microRNA (miRNA) family members are abundantly expressed, and some have recently been shown to serve as TLR7 ligands. We investigated whether let-7 miRNA family members differentially control microglia biology in health and disease. We found that a subset of let-7 miRNA family members function as signaling molecules to induce microglial release of inflammatory cytokines, modulate antigen presentation, and attenuate cell migration in a TLR7-dependent manner. The capability of the let-7 miRNAs to control microglial function is sequence specific, mapping to a let-7 …

Assessing Somatization In Urologic Chronic Pelvic Pain Syndrome, C S North, B A Hong, H H Lai, D H Alpers

Open Access Publications

BACKGROUND: This study examined the prevalence of somatization disorder in Urological Chronic Pelvic Pain Syndrome (UCPPS) and the utility of two self-report symptom screening tools for assessment of somatization in patients with UCPPS.

METHODS: The study sample included 65 patients with UCPPS who enrolled in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Study at Washington University. Patients completed the PolySymptomatic PolySyndromic Questionnaire (PSPS-Q) (n = 64) and the Patient Health Questionnaire-15 Somatic Symptom Severity Scale (PHQ-15) (n = 50). Review of patient medical records found that only 47% (n = 30) contained sufficient documentation to assess …

Discordant Transmission Of Bacteria And Viruses From Mothers To Babies At Birth, Rabia Maqsood, Rachel Rodgers, Cynthia Rodriguez, Scott A Handley, I. Malick Ndao, Phillip I Tarr, Barbara B Warner, Efrem S Lim, Lori R Holtz

Open Access Publications

BACKGROUND: The earliest microbial colonizers of the human gut can have life-long consequences for their hosts. Precisely how the neonatal gut bacterial microbiome and virome are initially populated is not well understood. To better understand how the maternal gut microbiome influences acquisition of the infant gut microbiome, we studied the early life bacterial microbiomes and viromes of 28 infant twin pairs and their mothers.

RESULTS: Infant bacterial and viral communities more closely resemble those of their related co-twin than unrelated infants. We found that 63% of an infant's bacterial microbiome can be traced to their mother's gut microbiota. In contrast, …

Lime-Induced Phytophotodermatitis, Ashraf Abugroun, Safwan Gaznabi, Arjun Natarajan, Hussein Daoud

Open Access Publications

Phytophotodermatitis, also commonly known as phototoxic dermatitis, is a common skin condition that occurs after contact with certain plants and subsequent exposure to sunlight. It is often confused with skin burns due to the blistering nature of its lesions. We herein report a case of phytophotodermatitis that developed in a 26-year-old male following contact with lime and subsequent exposure to sunlight.

The Local Translation Of Kna In Dendritic Projections Of Auditory Neurons And The Roles Of Kna In The Transition From Hidden To Overt Hearing Loss, Jeong Han Lee, Mincheol Kang, Seojin Park, Maria C. Perez-Flores, Xiao-Dong Zhang, Wenying Wang, Michael Anne Gratton, Nipavan Chiamvimonvat, Ebenezer N. Yamoah

Open Access Publications

Local and privileged expression of dendritic proteins allows segregation of distinct functions in a single neuron but may represent one of the underlying mechanisms for early and insidious presentation of sensory neuropathy. Tangible characteristics of early hearing loss (HL) are defined in correlation with nascent hidden hearing loss (HHL) in humans and animal models. Despite the plethora of causes of HL, only two prevailing mechanisms for HHL have been identified, and in both cases, common structural deficits are implicated in inner hair cell synapses, and demyelination of the auditory nerve (AN). We uncovered that Na

Rapid And Sustained Response To Immune Checkpoint Inhibition In Cutaneous Squamous Cell Carcinoma After Allogenic Hematopoietic Cell Transplant For Sézary Syndrome, Karam Khaddour, Amy Musiek, Lynn A Cornelius, Farrokh Dehdashti, Peter Westervelt, Ryan Fields, George Ansstas

2010-2019 OA Pubs

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is not uncommon in association with indolent malignancies that were treated with prior radiotherapy and after allogenic bone marrow transplantation. On the other hand, cutaneous T-cell lymphoma (CTCL) is a subtype of non-Hodgkin's lymphoma which is characterized by an indolent course, with relative refractoriness to conventional chemotherapies and radiotherapy, and occasionally referred for allogeneic hematopoietic cell transplantation (allo-HCT). Recently, the use of immune checkpoint inhibitors has gained attention in the treatment of both cutaneous squamous cell carcinoma and hematological malignancies. However, many patients with hematological malignancies eventually undergo allo-HCT, raising the concern of potential …

Text-Mining Clinically Relevant Cancer Biomarkers For Curation Into The Civic Database, Jake Lever, Martin R Jones, Arpad M Danos, Kilannin Krysiak, Melika Bonakdar, Jasleen K Grewal, Luka Culibrk, Obi L Griffith, Malachi Griffith, Steven J M Jones

Open Access Publications

BACKGROUND: Precision oncology involves analysis of individual cancer samples to understand the genes and pathways involved in the development and progression of a cancer. To improve patient care, knowledge of diagnostic, prognostic, predisposing, and drug response markers is essential. Several knowledgebases have been created by different groups to collate evidence for these associations. These include the open-access Clinical Interpretation of Variants in Cancer (CIViC) knowledgebase. These databases rely on time-consuming manual curation from skilled experts who read and interpret the relevant biomedical literature.

METHODS: To aid in this curation and provide the greatest coverage for these databases, particularly CIViC, we …

Developmental Hypomyelination In Wolfram Syndrome: New Insights From Neuroimaging And Gene Expression Analyses, Amjad Samara, Rachel Rahn, Olga Neyman, Ki Yun Park, Ahmad Samara, Bess Marshall, Joseph Dougherty, Tamara Hershey

Open Access Publications

Wolfram syndrome is a rare multisystem disorder caused by mutations in WFS1 or CISD2 genes leading to brain structural abnormalities and neurological symptoms. These abnormalities appear in early stages of the disease. The pathogenesis of Wolfram syndrome involves abnormalities in the endoplasmic reticulum (ER) and mitochondrial dynamics, which are common features in several other neurodegenerative disorders. Mutations in WFS1 are responsible for the majority of Wolfram syndrome cases. WFS1 encodes for an endoplasmic reticulum (ER) protein, wolframin. It is proposed that wolframin deficiency triggers the unfolded protein response (UPR) pathway resulting in an increased ER stress-mediated neuronal loss. Recent neuroimaging …

A Metastable Subproteome Underlies Inclusion Formation In Muscle Proteinopathies, Prajwal Ciryam, Matthew Antalek, Fernando Cid, Gian Gaetano Tartaglia, Christopher M Dobson, Anne-Katrin Guettsches, Britta Eggers, Matthias Vorgerd, Katrin Marcus, Rudolf A Kley, Richard I Morimoto, Michele Vendruscolo, Conrad C Weihl

Open Access Publications

Protein aggregation is a pathological feature of neurodegenerative disorders. We previously demonstrated that protein inclusions in the brain are composed of supersaturated proteins, which are abundant and aggregation-prone, and form a metastable subproteome. It is not yet clear, however, whether this phenomenon is also associated with non-neuronal protein conformational disorders. To respond to this question, we analyzed proteomic datasets from biopsies of patients with genetic and acquired protein aggregate myopathy (PAM) by quantifying the changes in composition, concentration and aggregation propensity of proteins in the fibers containing inclusions and those surrounding them. We found that a metastable subproteome is present …

Association Of Aspirin Use With Mortality Risk Among Older Adult Participants In The Prostate, Lung, Colorectal, And Ovarian Cancer Screening Trial, Holli A. Loomans-Kropp, Paul Pinsky, Yin Cao, Andrew T. Chan, Asad Umar

Open Access Publications

Importance: Aspirin use has been associated with reduced risk of cancer mortality, particularly of the colorectum. However, aspirin efficacy may be influenced by biological characteristics, such as obesity and age. With the increasing prevalence of obesity and conflicting data regarding the effect of aspirin in older adults, understanding the potential association of aspirin use with cancer mortality according to body mass index (BMI) and age is imperative.

Objectives: To investigate the association of aspirin use with risk of all-cause, any cancer, gastrointestinal (GI) cancer, and colorectal cancer (CRC) mortality among older adults and to perform an exploratory analysis of the …

Association Of Longitudinal Changes In Cerebrospinal Fluid Total Tau And Phosphorylated Tau 181 And Brain Atrophy With Disease Progression In Patients With Alzheimer Disease, Jorge J. Llibre-Guerra, Yan Li, Suzanne E. Schindler, Brian A. Gordon, Anne M. Fagan, John C. Morris, Tammie L.S. Benzinger, Jason Hassenstab, Sarah B. Berman, David M. Holtzman, Chengjie Xiong, Randall J. Bateman, Eric Mcdade

Open Access Publications

Importance: The amyloid/tau/neurodegeneration (A/T/N) framework uses cerebrospinal fluid (CSF) levels of total tau (tTau) as a marker of neurodegeneration and CSF levels of phosphorylated tau 181 (pTau181) as a marker of tau tangles. However, it is unclear whether CSF levels of tTau and pTau181 have similar or different trajectories over the course of Alzheimer disease.

Objectives: To examine the rates of change in CSF levels of tTau and pTau181 across the Alzheimer disease course and how the rates of change are associated with brain atrophy as measured by magnetic resonance imaging.

Design, Setting, and Participants: This cohort study was set …