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https://www.readbyqxmd.com/read/28133816/typical-and-atypical-pathology-in-primary-progressive-aphasia-variants
#1
Edoardo G Spinelli, Maria Luisa Mandelli, Zachary A Miller, Miguel A Santos-Santos, Stephen M Wilson, Federica Agosta, Lea T Grinberg, Eric J Huang, John Q Trojanowski, Marita Meyer, Maya L Henry, Giancarlo Comi, Gil Rabinovici, Howard J Rosen, Massimo Filippi, Bruce L Miller, William W Seeley, Maria Luisa Gorno-Tempini
OBJECTIVE: To characterize in vivo signatures of pathological diagnosis in a large cohort of patients with primary progressive aphasia (PPA) variants defined by current diagnostic classification. METHODS: Extensive clinical, cognitive, neuroimaging, and neuropathological data were collected from 69 patients with sporadic PPA, divided into 29 semantic (svPPA), 25 non-fluent (nfvPPA), 11 logopenic (lvPPA), and 4 mixed PPA. Patterns of grey matter (GM) and white matter (WM) atrophy at presentation were assessed and tested as predictors of pathological diagnosis using support vector machine (SVM) algorithms...
January 30, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28130473/frontotemporal-dementia-with-the-v337m-mapt-mutation-tau-pet-and-pathology-correlations
#2
Salvatore Spina, Daniel R Schonhaut, Bradley F Boeve, William W Seeley, Rik Ossenkoppele, James P O'Neil, Andreas Lazaris, Howard J Rosen, Adam L Boxer, David C Perry, Bruce L Miller, Dennis W Dickson, Joseph E Parisi, William J Jagust, Melissa E Murray, Gil D Rabinovici
OBJECTIVE: To assess the efficacy of [(18)F]AV1451 PET in visualizing tau pathology in vivo in a patient with frontotemporal dementia (FTD) associated with the V337M microtubule-associated protein tau (MAPT) mutation. METHODS: MAPT mutations are associated with the deposition of hyperphosphorylated tau protein in neurons and glia. The PET tracer [(18)F]AV1451 binds with high affinity to paired helical filaments tau that comprises neurofibrillary tangles in Alzheimer disease (AD), while postmortem studies suggest lower or absent binding to the tau filaments of the majority of non-AD tauopathies...
January 27, 2017: Neurology
https://www.readbyqxmd.com/read/28117917/quantifying-the-accretion-of-hyperphosphorylated-tau-in-the-locus-coeruleus-and-dorsal-raphe-nucleus-the-pathological-building-blocks-of-early-alzheimer-s-disease
#3
Alexander J Ehrenberg, Austin K Nguy, Panos Theofilas, Sara Dunlop, Claudia K Suemoto, Ana T D L Alho, Renata Paraizo Leite, Roberta Diehl Rodriguez, Maria B Mejia, Udo Rüb, Jose M Farfel, Renata Eloah de Lucena Ferretti-Rebustini, Camila F Nascimento, Ricardo Nitrini, Carlos Augusto Pasquallucci, Wilson Jacob-Filho, Bruce Miller, William W Seeley, Helmut Heinsen, Lea T Grinberg
AIMS: Hyperphosphorylated tau-neuronal cytoplasmic inclusions (ht-NCI) are the best protein correlate of clinical decline in Alzheimer's disease (AD). Qualitative evidence identifies ht-NCI accumulating in the isodendritic core before the entorhinal cortex. Here, we used unbiased stereology to quantify ht-NCI burden in the locus coeruleus and dorsal raphe nucleus, aiming to characterize the impact of AD pathology in these nuclei with a focus on early stages. METHODS: We utilized unbiased stereology in a sample of 48 well-characterized subjects enriched for controls and early AD stages...
January 24, 2017: Neuropathology and Applied Neurobiology
https://www.readbyqxmd.com/read/28113724/brain-modulyzer-interactive-visual-analysis-of-functional-brain-connectivity
#4
Sugeerth Murugesan, Kristofer Bouchard, Jesse A Brown, Bernd Hamann, William W Seeley, Andrew Trujillo, Gunther H Weber
We present Brain Modulyzer, an interactive visual exploration tool for functional magnetic resonance imaging (fMRI) brain scans, aimed at analyzing the correlation between different brain regions when resting or when performing mental tasks. Brain Modulyzer combines multiple coordinated views-such as heat maps, node link diagrams and anatomical views-using brushing and linking to provide an anatomical context for brain connectivity data. Integrating methods from graph theory and analysis, e.g., community detection and derived graph measures, makes it possible to explore the modular and hierarchical organization of functional brain networks...
May 9, 2016: IEEE/ACM Transactions on Computational Biology and Bioinformatics
https://www.readbyqxmd.com/read/28072389/suppression-of-c9orf72-rna-repeat-induced-neurotoxicity-by-the-als-associated-rna-binding-protein-zfp106
#5
Barbara Celona, John von Dollen, Sarat C Vatsavayai, Risa Kashima, Jeffrey R Johnson, Amy A Tang, Akiko Hata, Bruce L Miller, Eric J Huang, Nevan J Krogan, William W Seeley, Brian L Black
Expanded GGGGCC repeats in the first intron of the C9orf72 gene represent the most common cause of familial amyotrophic lateral sclerosis (ALS), but the mechanisms underlying repeat-induced disease remain incompletely resolved. One proposed gain-of-function mechanism is that repeat-containing RNA forms aggregates that sequester RNA binding proteins, leading to altered RNA metabolism in motor neurons. Here, we identify the zinc finger protein Zfp106 as a specific GGGGCC RNA repeat-binding protein, and using affinity purification-mass spectrometry, we show that Zfp106 interacts with multiple other RNA binding proteins, including the ALS-associated factors TDP-43 and FUS...
January 10, 2017: ELife
https://www.readbyqxmd.com/read/28040670/focal-temporal-pole-atrophy-and-network-degeneration-in-semantic-variant-primary-progressive-aphasia
#6
Jessica A Collins, Victor Montal, Daisy Hochberg, Megan Quimby, Maria Luisa Mandelli, Nikos Makris, William W Seeley, Maria Luisa Gorno-Tempini, Bradford C Dickerson
A wealth of neuroimaging research has associated semantic variant primary progressive aphasia with distributed cortical atrophy that is most prominent in the left anterior temporal cortex; however, there is little consensus regarding which region within the anterior temporal cortex is most prominently damaged, which may indicate the putative origin of neurodegeneration. In this study, we localized the most prominent and consistent region of atrophy in semantic variant primary progressive aphasia using cortical thickness analysis in two independent patient samples (n = 16 and 28, respectively) relative to age-matched controls (n = 30)...
February 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28035008/regulator-of-g-protein-signaling-6-protects-the-heart-from-ischemic-injury
#7
Boyd R Rorabaugh, Bandana Chakravarti, Nathaniel W Mabe, Sarah L Seeley, Albert D Bui, Jianqi Yang, Stephanie W Watts, Richard R Neubig, Rory A Fisher
Gαi-coupled receptors play important roles in protecting the heart from ischemic injury. Regulator of G protein signaling (RGS) proteins suppress Gαi signaling by accelerating the GTPase activity of Gαi subunits. However, the roles of individual RGS proteins in modulating ischemic injury are unknown. In the present study, we investigated the impact of RGS6 deletion on myocardial sensitivity to ischemic injury. Hearts from RGS6 knockout (RGS6-/-) and wildtype (RGS6+/+) mice were subjected to 30 min ischemia and 2 hr reperfusion on a Langendorff heart apparatus...
December 29, 2016: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27981028/regional-correlations-between-11-c-pib-pet-and-post-mortem-burden-of-amyloid-beta-pathology-in-a-diverse-neuropathological-cohort
#8
Sang Won Seo, Nagehan Ayakta, Lea T Grinberg, Sylvia Villeneuve, Manja Lehmann, Bruce Reed, Charles DeCarli, Bruce L Miller, Howard J Rosen, Adam L Boxer, James P O'Neil, Lee-Way Jin, William W Seeley, William J Jagust, Gil D Rabinovici
Imaging-pathological correlation studies show that in vivo amyloid-β (Aβ) positron emission tomography (PET) strongly predicts the presence of significant Aβ pathology at autopsy. We sought to determine whether regional PiB-PET uptake would improve sensitivity for amyloid detection in comparison with global measures (experiment 1), and to estimate the relative contributions of different Aβ aggregates to in vivo PET signal (experiment 2). In experiment 1, 54 subjects with [(11)C] PiB-PET during life and postmortem neuropathologic examination (85...
2017: NeuroImage: Clinical
https://www.readbyqxmd.com/read/27913432/von-economo-neurons-and-fork-cells-a-neurochemical-signature-linked-to-monoaminergic-function
#9
Anke A Dijkstra, Li-Chun Lin, Alissa L Nana, Stephanie E Gaus, William W Seeley
The human anterior cingulate and frontoinsular cortices are distinguished by 2 unique Layer 5 neuronal morphotypes, the von Economo neurons (VENs) and fork cells, whose biological identity remains mysterious. Insights could impact research on diverse neuropsychiatric diseases to which these cells have been linked. Here, we leveraged the Allen Brain Atlas to evaluate mRNA expression of 176 neurotransmitter-related genes and identified vesicular monoamine transporter 2 (VMAT2), gamma-aminobutyric acid (GABA) receptor subunit θ (GABRQ), and adrenoreceptor α-1A (ADRA1A) expression in human VENs, fork cells, and a minority of neighboring Layer 5 neurons...
December 1, 2016: Cerebral Cortex
https://www.readbyqxmd.com/read/27911827/tau-prions-from-alzheimer-s-disease-and-chronic-traumatic-encephalopathy-patients-propagate-in-cultured-cells
#10
Amanda L Woerman, Atsushi Aoyagi, Smita Patel, Sabeen A Kazmi, Iryna Lobach, Lea T Grinberg, Ann C McKee, William W Seeley, Steven H Olson, Stanley B Prusiner
Tau prions are thought to aggregate in the central nervous system, resulting in neurodegeneration. Among the tauopathies, Alzheimer's disease (AD) is the most common, whereas argyrophilic grain disease (AGD), corticobasal degeneration (CBD), chronic traumatic encephalopathy (CTE), Pick's disease (PiD), and progressive supranuclear palsy (PSP) are less prevalent. Brain extracts from deceased individuals with PiD, a neurodegenerative disorder characterized by three-repeat (3R) tau prions, were used to infect HEK293T cells expressing 3R tau fused to yellow fluorescent protein (YFP)...
December 13, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27844039/increased-prevalence-of-autoimmune-disease-within-c9-and-ftd-mnd-cohorts-completing-the-picture
#11
Zachary A Miller, Virginia E Sturm, Gamze Balci Camsari, Anna Karydas, Jennifer S Yokoyama, Lea T Grinberg, Adam L Boxer, Howard J Rosen, Katherine P Rankin, Maria Luisa Gorno-Tempini, Giovanni Coppola, Daniel H Geschwind, Rosa Rademakers, William W Seeley, Neill R Graff-Radford, Bruce L Miller
OBJECTIVE: To determine the prevalence of autoimmune disease in symptomatic C9ORF72 (C9) mutation carriers and frontotemporal dementia with motor neuron disease (FTD/MND) cohorts. METHODS: In this case-control study, we reviewed the clinical histories of 66 patients with FTD/MND and 57 symptomatic C9 carriers (24 overlapping cases), a total of 99 charts, for history of autoimmune disease. The prevalence of autoimmune disease in C9 and FTD/MND cohorts was determined by χ(2) and Fisher exact comparisons between the combined C9 and FTD/MND group with normal control, Alzheimer disease, and progressive supranuclear palsy cohorts, as well as comparisons within C9 and FTD/MND cohorts...
December 2016: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/27799513/smoking-cessation-version-1-2016-nccn-clinical-practice-guidelines-in-oncology
#12
Peter G Shields, Roy S Herbst, Douglas Arenberg, Neal L Benowitz, Laura Bierut, Julie Bylund Luckart, Paul Cinciripini, Bradley Collins, Sean David, James Davis, Brian Hitsman, Andrew Hyland, Margaret Lang, Scott Leischow, Elyse R Park, W Thomas Purcell, Jill Selzle, Andrea Silber, Sharon Spencer, Tawee Tanvetyanon, Brian Tiep, Hilary A Tindle, Reginald Tucker-Seeley, James Urbanic, Monica Webb Hooper, Benny Weksler, C Will Whitlock, Douglas E Wood, Jennifer Burns, Jillian Scavone
Cigarette smoking has been implicated in causing many cancers and cancer deaths. There is mounting evidence indicating that smoking negatively impacts cancer treatment efficacy and overall survival. The NCCN Guidelines for Smoking Cessation have been created to emphasize the importance of smoking cessation and establish an evidence-based standard of care in all patients with cancer. These guidelines provide recommendations to address smoking in patients and outlines behavioral and pharmacologic interventions for smoking cessation throughout the continuum of oncology care...
November 2016: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/27797809/timing-and-significance-of-pathological-features-in-c9orf72-expansion-associated-frontotemporal-dementia
#13
Sarat C Vatsavayai, Soo Jin Yoon, Raquel C Gardner, Tania F Gendron, Jose Norberto S Vargas, Andrew Trujillo, Mochtar Pribadi, Joanna J Phillips, Stephanie E Gaus, John D Hixson, Paul A Garcia, Gil D Rabinovici, Giovanni Coppola, Daniel H Geschwind, Leonard Petrucelli, Bruce L Miller, William W Seeley
SEE SCABER AND TALBOT DOI101093/AWW264 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: A GGGGCC repeat expansion in C9orf72 leads to frontotemporal dementia and/or amyotrophic lateral sclerosis. Diverse pathological features have been identified, and their disease relevance remains much debated. Here, we describe two illuminating patients with frontotemporal dementia due to the C9orf72 repeat expansion. Case 1 was a 65-year-old female with behavioural variant frontotemporal dementia accompanied by focal degeneration in subgenual anterior cingulate cortex, amygdala, and medial pulvinar thalamus...
December 2016: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/27714549/systemic-klotho-is-associated-with-klotho-variation-and-predicts-intrinsic-cortical-connectivity-in-healthy-human-aging
#14
Jennifer S Yokoyama, Gabe Marx, Jesse A Brown, Luke W Bonham, Dan Wang, Giovanni Coppola, William W Seeley, Howard J Rosen, Bruce L Miller, Joel H Kramer, Dena B Dubal
Cognitive decline is a major biomedical challenge as the global population ages. Elevated levels of the longevity factor klotho suppress aging, enhance cognition, and promote synaptic plasticity and neural resilience against aging and Alzheimer's disease (AD)-related pathogenic proteins. Here, we examined the relationship between human genetic variants of KLOTHO and systemic klotho levels - and assessed neuroanatomic correlates of serum klotho in a cohort of healthy older adults. Serum klotho levels were increased with KL-VS heterozygosity, as anticipated...
October 6, 2016: Brain Imaging and Behavior
https://www.readbyqxmd.com/read/27698154/cognition-and-neuropsychiatry-in-behavioral-variant-frontotemporal-dementia-by-disease-stage
#15
Maxime Bertoux, Marie Sarazin, Florence Pasquier, Michel Bottlaender, Leonardo Cruz de Souza, Eneida Mioshi, Michael Hornberger, Kamalini G Ranasinghe, Katherine P Rankin, Iryna V Lobach, Joel H Kramer, Virginia E Sturm, Brianne M Bettcher, Katherine Possin, S Christine You, Amanda K Lamarre, Tal Shany-Ur, Melanie L Stephens, David C Perry, Suzee E Lee, Zachary A Miller, Maria L Gorno-Tempini, Howard J Rosen, Adam Boxer, William W Seeley, Gil D Rabinovici, Keith A Vossel, Bruce L Miller
No abstract text is available yet for this article.
October 4, 2016: Neurology
https://www.readbyqxmd.com/read/27632828/effects-of-experimental-anterior-knee-pain-on-muscle-activation-during-landing-and-jumping-performed-at-various-intensities
#16
Jihong Park, W Matt Denning, Jordan D Pitt, Devin Francom, J Ty Hopkins, Matthew K Seeley
CONTEXT: Although knee pain is common, some facets of this pain are unclear. The independent effects (i.e., independent from other knee injury or pathology) of knee pain on neural activation of lower-extremity muscles during landing and jumping have not been observed. OBJECTIVE: To investigate the independent effects of knee pain on lower-extremity muscle (gastrocnemius, vastus medialis, medial hamstrings, gluteus medius, and gluteus maximus) activation amplitude during landing and jumping, performed at two different intensities...
August 24, 2016: Journal of Sport Rehabilitation
https://www.readbyqxmd.com/read/27518780/paracentric-inversion-of-chromosome-21-leading-to-disruption-of-the-hlcs-gene-in-a-family-with-holocarboxylase-synthetase-deficiency
#17
Shane C Quinonez, Andrea H Seeley, Cindy Lam, Thomas W Glover, Bruce A Barshop, Catherine E Keegan
Holocarboxylase synthetase (HLCS) deficiency is a rare autosomal recessive disorder that presents with multiple life-threatening metabolic derangements including metabolic acidosis, ketosis, and hyperammonemia. A majority of HLCS deficiency patients respond to biotin therapy; however, some patients show only a partial or no response to biotin therapy. Here, we report a neonatal presentation of HLCS deficiency with partial response to biotin therapy. Sequencing of HLCS showed a novel heterozygous mutation in exon 5, c...
August 13, 2016: JIMD Reports
https://www.readbyqxmd.com/read/27513978/locus-coeruleus-volume-and-cell-population-changes-during-alzheimer-s-disease-progression-a-stereological-study-in-human-postmortem-brains-with-potential-implication-for-early-stage-biomarker-discovery
#18
Panos Theofilas, Alexander J Ehrenberg, Sara Dunlop, Ana T Di Lorenzo Alho, Austin Nguy, Renata Elaine Paraizo Leite, Roberta Diehl Rodriguez, Maria B Mejia, Claudia K Suemoto, Renata Eloah De Lucena Ferretti-Rebustini, Livia Polichiso, Camila F Nascimento, William W Seeley, Ricardo Nitrini, Carlos Augusto Pasqualucci, Wilson Jacob Filho, Udo Rueb, John Neuhaus, Helmut Heinsen, Lea T Grinberg
INTRODUCTION: Alzheimer's disease (AD) progression follows a specific spreading pattern, emphasizing the need to characterize those brain areas that degenerate first. The brainstem's locus coeruleus (LC) is the first area to develop neurofibrillary changes (neurofibrillary tangles [NFTs]). METHODS: The methods include unbiased stereological analyses in human brainstems to estimate LC volume and neuronal population in controls and individuals across all AD stages...
August 8, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/27497488/healthy-brain-connectivity-predicts-atrophy-progression-in-non-fluent-variant-of-primary-progressive-aphasia
#19
Maria Luisa Mandelli, Eduard Vilaplana, Jesse A Brown, H Isabel Hubbard, Richard J Binney, Suneth Attygalle, Miguel A Santos-Santos, Zachary A Miller, Mikhail Pakvasa, Maya L Henry, Howard J Rosen, Roland G Henry, Gil D Rabinovici, Bruce L Miller, William W Seeley, Maria Luisa Gorno-Tempini
Neurodegeneration has been hypothesized to follow predetermined large-scale networks through the trans-synaptic spread of toxic proteins from a syndrome-specific epicentre. To date, no longitudinal neuroimaging study has tested this hypothesis in vivo in frontotemporal dementia spectrum disorders. The aim of this study was to demonstrate that longitudinal progression of atrophy in non-fluent/agrammatic variant primary progressive aphasia spreads over time from a syndrome-specific epicentre to additional regions, based on their connectivity to the epicentre in healthy control subjects...
October 2016: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/27429218/distinct-subtypes-of-behavioral-variant-frontotemporal-dementia-based-on-patterns-of-network-degeneration
#20
Kamalini G Ranasinghe, Katherine P Rankin, Peter S Pressman, David C Perry, Iryna V Lobach, William W Seeley, Giovanni Coppola, Anna M Karydas, Lea T Grinberg, Tal Shany-Ur, Suzee E Lee, Gil D Rabinovici, Howard J Rosen, Maria Luisa Gorno-Tempini, Adam L Boxer, Zachary A Miller, Winston Chiong, Mary DeMay, Joel H Kramer, Katherine L Possin, Virginia E Sturm, Brianne M Bettcher, Michael Neylan, Diana D Zackey, Lauren A Nguyen, Robin Ketelle, Nikolas Block, Teresa Q Wu, Alison Dallich, Natanya Russek, Alyssa Caplan, Daniel H Geschwind, Keith A Vossel, Bruce L Miller
IMPORTANCE: Clearer delineation of the phenotypic heterogeneity within behavioral variant frontotemporal dementia (bvFTD) will help uncover underlying biological mechanisms and improve clinicians' ability to predict disease course and to design targeted management strategies. OBJECTIVE: To identify subtypes of bvFTD syndrome based on distinctive patterns of atrophy defined by selective vulnerability of specific functional networks targeted in bvFTD using statistical classification approaches...
September 1, 2016: JAMA Neurology
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