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Author Gabor G Kovacs

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Biomarkers and diagnostic guidelines for sporadic Creutzfeldt-Jakob disease.

Peter Hermann, Brian Appleby, Jean-Philippe Brandel, Byron Caughey, Steven Collins, Michael D Geschwind, Alison Green, Stephane Haïk, Gabor G Kovacs, Anna Ladogana, Franc Llorens, Simon Mead, Noriyuki Nishida, Suvankar Pal, Piero Parchi, Maurizio Pocchiari, Katsuya Satoh, Gianluigi Zanusso, Inga Zerr,

Sporadic Creutzfeldt-Jakob disease is a fatal neurodegenerative disease caused by misfolded prion proteins (PrP<sup>Sc</sup>). Effective therapeutics are currently not available and accurate diagnosis can be challenging. Clinical diagnostic criteria use a combination of characteristic neuropsychiatric symptoms, CSF proteins 14-3-3, MRI, and EEG. Supportive biomarkers, such as high CSF total tau, ... Read more >>

Lancet Neurol (The Lancet. Neurology)
[2021, 20(3):235-246]

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Early Selective Vulnerability of the CA2 Hippocampal Subfield in Primary Age-Related Tauopathy.

Jamie M Walker, Timothy E Richardson, Kurt Farrell, Megan A Iida, Chan Foong, Ping Shang, Johannes Attems, Gai Ayalon, Thomas G Beach, Eileen H Bigio, Andrew Budson, Nigel J Cairns, María Corrada, Etty Cortes, Dennis W Dickson, Peter Fischer, Margaret E Flanagan, Erin Franklin, Marla Gearing, Jonathan Glass, Lawrence A Hansen, Vahram Haroutunian, Patrick R Hof, Lawrence Honig, Claudia Kawas, C Dirk Keene, Julia Kofler, Gabor G Kovacs, Edward B Lee, Mirjam I Lutz, Qinwen Mao, Eliezer Masliah, Ann C McKee, Corey T McMillan, M Marsel Mesulam, Melissa Murray, Peter T Nelson, Richard Perrin, Thao Pham, Wayne Poon, Dushyant P Purohit, Robert A Rissman, Kenji Sakai, Mary Sano, Julie A Schneider, Thor D Stein, Andrew F Teich, John Q Trojanowski, Juan C Troncoso, Jean-Paul Vonsattel, Sandra Weintraub, David A Wolk, Randall L Woltjer, Masahito Yamada, Lei Yu, Charles L White, John F Crary,

Primary age-related tauopathy (PART) is a neurodegenerative entity defined as Alzheimer-type neurofibrillary degeneration primarily affecting the medial temporal lobe with minimal to absent amyloid-β (Aβ) plaque deposition. The extent to which PART can be differentiated pathoanatomically from Alzheimer disease (AD) is unclear. Here, we examined the regional distribution of tau ... Read more >>

J Neuropathol Exp Neurol (Journal of neuropathology and experimental neurology)
[2021, 80(2):102-111]

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Neuropathological consensus criteria for the evaluation of Lewy pathology in post-mortem brains: a multi-centre study.

Johannes Attems, Jon B Toledo, Lauren Walker, Ellen Gelpi, Steve Gentleman, Glenda Halliday, Tibor Hortobagyi, Kurt Jellinger, Gabor G Kovacs, Edward B Lee, Seth Love, Kirsty E McAleese, Peter T Nelson, Manuela Neumann, Laura Parkkinen, Tuomo Polvikoski, Beata Sikorska, Colin Smith, Lea Tenenholz Grinberg, Dietmar R Thal, John Q Trojanowski, Ian G McKeith,

Currently, the neuropathological diagnosis of Lewy body disease (LBD) may be stated according to several staging systems, which include the Braak Lewy body stages (Braak), the consensus criteria by McKeith and colleagues (McKeith), the modified McKeith system by Leverenz and colleagues (Leverenz), and the Unified Staging System by Beach and ... Read more >>

Acta Neuropathol (Acta neuropathologica)
[2021, 141(2):159-172]

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A novel temporal-predominant neuro-astroglial tauopathy associated with TMEM106B gene polymorphism in FTLD/ALS-TDP.

Jorge J Llibre-Guerra, Suzee E Lee, Claudia K Suemoto, Alexander J Ehrenberg, Gabor G Kovacs, Anna Karydas, Adam Staffaroni, Elisa De Paula Franca Resende, Eun-Joo Kim, Ji-Hye Hwang, Eliana Marisa Ramos, Kevin J Wojta, Lorenzo Pasquini, Shirley Yin-Yu Pang, Salvatore Spina, Isabel E Allen, Joel Kramer, Bruce L Miller, William W Seeley, Lea T Grinberg,

Polymorphisms in TMEM106B, a gene on chromosome 7p21.3 involved in lysosomal trafficking, correlates to worse neuropathological, and clinical outcomes in frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) with TDP-43 inclusions. In a small cohort of C9orf72 expansion carriers, we previously found an atypical, neuroglial tauopathy in cases harboring ... Read more >>

Brain Pathol (Brain pathology (Zurich, Switzerland))
[2020, :e12924]

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Multiple system aging-related tau astrogliopathy with complex proteinopathy in an oligosymptomatic octogenarian.

Sigrid Klotz, Peter Fischer, Margareta Hinterberger, Gerda Ricken, Selma Hönigschnabl, Ellen Gelpi, Gabor G Kovacs,

The combination of multiple neurodegenerative proteinopathies is increasingly recognized. Together they can potentiate neuronal dysfunction and contribute to complex neurological symptoms. We report an octogenarian female case of multiple extraneural metastases of a rectal carcinoma. She attempted suicide, which ultimately led to cardiorespiratory failure nine days after hospital admission. Apart from ... Read more >>

Neuropathology (Neuropathology : official journal of the Japanese Society of Neuropathology)
[2021, 41(1):72-83]

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Co-incidental C9orf72 expansion mutation-related frontotemporal lobar degeneration pathology and sporadic Creutzfeldt-Jakob disease.

Sigrid Klotz, Theresa König, Marcus Erdler, Andreas Ulram, Anita Nguyen, Thomas Ströbel, Alexander Zimprich, Elisabeth Stögmann, Günther Regelsberger, Romana Höftberger, Herbert Budka, Gabor G Kovacs, Ellen Gelpi,

<h4>Background</h4>The C9orf72 hexanucleotide expansion mutation is the most common cause of genetic frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS) and combined FTD-ALS. Its underlying neuropathology combines TDP-43 pathology and dipeptide repeat protein (DPR) deposits and may also associate with other neurodegeneration-associated protein aggregates. Herein we present a unique combination of ... Read more >>

Eur J Neurol (European journal of neurology)
[2021, 28(3):1009-1015]

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Novel dominant MPAN family with a complex genetic architecture as a basis for phenotypic variability.

Peter Balicza, Renata Bencsik, Andras Lengyel, Aniko Gal, Zoltan Grosz, Dora Csaban, Gabor Rudas, Krisztina Danics, Gabor G Kovacs, Maria Judit Molnar,

<h4>Objective</h4>Our aim was to study a Hungarian family with autosomal dominantly inherited neurodegeneration with brain iron accumulation (NBIA) with markedly different intrafamilial expressivity.<h4>Methods</h4>Targeted sequencing and multiplex ligation-dependent probe amplification (MLPA) of known NBIA-associated genes were performed in many affected and unaffected members of the family. In addition, a trio whole-genome ... Read more >>

Neurol Genet (Neurology. Genetics)
[2020, 6(5):e515]

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Identification of novel risk loci and causal insights for sporadic Creutzfeldt-Jakob disease: a genome-wide association study.

Emma Jones, Holger Hummerich, Emmanuelle Viré, James Uphill, Athanasios Dimitriadis, Helen Speedy, Tracy Campbell, Penny Norsworthy, Liam Quinn, Jerome Whitfield, Jacqueline Linehan, Zane Jaunmuktane, Sebastian Brandner, Parmjit Jat, Akin Nihat, Tze How Mok, Parvin Ahmed, Steven Collins, Christiane Stehmann, Shannon Sarros, Gabor G Kovacs, Michael D Geschwind, Aili Golubjatnikov, Karl Frontzek, Herbert Budka, Adriano Aguzzi, Hata Karamujić-Čomić, Sven J van der Lee, Carla A Ibrahim-Verbaas, Cornelia M van Duijn, Beata Sikorska, Ewa Golanska, Pawel P Liberski, Miguel Calero, Olga Calero, Pascual Sanchez-Juan, Antonio Salas, Federico Martinón-Torres, Elodie Bouaziz-Amar, Stéphane Haïk, Jean-Louis Laplanche, Jean-Phillipe Brandel, Phillipe Amouyel, Jean-Charles Lambert, Piero Parchi, Anna Bartoletti-Stella, Sabina Capellari, Anna Poleggi, Anna Ladogana, Maurizio Pocchiari, Serena Aneli, Giuseppe Matullo, Richard Knight, Saima Zafar, Inga Zerr, Stephanie Booth, Michael B Coulthart, Gerard H Jansen, Katie Glisic, Janis Blevins, Pierluigi Gambetti, Jiri Safar, Brian Appleby, John Collinge, Simon Mead,

<h4>Background</h4>Human prion diseases are rare and usually rapidly fatal neurodegenerative disorders, the most common being sporadic Creutzfeldt-Jakob disease (sCJD). Variants in the PRNP gene that encodes prion protein are strong risk factors for sCJD but, although the condition has similar heritability to other neurodegenerative disorders, no other genetic risk loci ... Read more >>

Lancet Neurol (The Lancet. Neurology)
[2020, 19(10):840-848]

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Neuronal intranuclear inclusion disease is genetically heterogeneous.

Zhongbo Chen, Wai Yan Yau, Zane Jaunmuktane, Arianna Tucci, Prasanth Sivakumar, Sarah A Gagliano Taliun, Chris Turner, Stephanie Efthymiou, Kristina Ibáñez, Roisin Sullivan, Farah Bibi, Alkyoni Athanasiou-Fragkouli, Thomas Bourinaris, David Zhang, Tamas Revesz, Tammaryn Lashley, Michael DeTure, Dennis W Dickson, Keith A Josephs, Ellen Gelpi, Gabor G Kovacs, Glenda Halliday, Dominic B Rowe, Ian Blair, Pentti J Tienari, Anu Suomalainen, Nick C Fox, Nicholas W Wood, Andrew J Lees, Matti J Haltia, , John Hardy, Mina Ryten, Jana Vandrovcova, Henry Houlden,

Neuronal intranuclear inclusion disease (NIID) is a clinically heterogeneous neurodegenerative condition characterized by pathological intranuclear eosinophilic inclusions. A CGG repeat expansion in NOTCH2NLC was recently identified to be associated with NIID in patients of Japanese descent. We screened pathologically confirmed European NIID, cases of neurodegenerative disease with intranuclear inclusions and ... Read more >>

Ann Clin Transl Neurol (Annals of clinical and translational neurology)
[2020, 7(9):1716-1725]

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Clinicopathological Relationships in an Aged Case of DOORS Syndrome With a p.Arg506X Mutation in the ATP6V1B2 Gene.

Dénes Zádori, Levente Szalárdy, Zita Reisz, Gabor G Kovacs, Rita Maszlag-Török, Norbert F Ajeawung, László Vécsei, Philippe M Campeau, Péter Klivényi,

DOORS [deafness, onychodystrophy, osteodystrophy, intellectual disability (mental retardation), and seizures] syndrome can be caused by mutations in the <i>TBC1D24</i> and <i>ATP6V1B2</i> genes, both of which are involved in endolysosomal function. Because of its extreme rarity, to date, no detailed neuropathological assessment has been performed to establish clinicopathological relationships and, thereby, ... Read more >>

Front Neurol (Frontiers in neurology)
[2020, 11:767]

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Practical Considerations in the Diagnosis of Mild Chronic Traumatic Encephalopathy and Distinction From Age-Related Tau Astrogliopathy.

Ann C McKee, Thor D Stein, John F Crary, Kevin F Bieniek, Robert C Cantu, Gabor G Kovacs,

J Neuropathol Exp Neurol (Journal of neuropathology and experimental neurology)
[2020, 79(8):921-924]

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Thorn-shaped astrocytes in the depth of cortical sulci in Western Pacific ALS/Parkinsonism-Dementia complex.

Gabor G Kovacs, John L Robinson, Daniel P Perl, Virginia M-Y Lee, John Q Trojanowski,

Acta Neuropathol (Acta neuropathologica)
[2020, 140(4):591-593]

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Hereditary ATTR Amyloidosis in Austria: Prevalence and Epidemiological Hot Spots.

Michaela Auer-Grumbach, Rene Rettl, Klemens Ablasser, Hermine Agis, Christian Beetz, Franz Duca, Martin Gattermeier, Franz Glaser, Markus Hacker, Renate Kain, Birgit Kaufmann, Gabor G Kovacs, Christian Lampl, Neira Ljevakovic, Jutta Nagele, Gerhard Pölzl, Stefan Quasthoff, Bernadette Raimann, Helmut Rauschka, Christian Reiter, Volha Skrahina, Othmar Schuhfried, Raute Sunder-Plassmann, Nicolas D Verheyen, Julia Wanschitz, Thomas Weber, Reinhard Windhager, Raphael Wurm, Friedrich Zimprich, Wolfgang N Löscher, Diana Bonderman,

<h4>Background</h4>Hereditary transthyretin amyloidosis (hATTR) is an autosomal dominantly inherited disorder caused by an accumulation of amyloid fibrils in tissues due to mutations in the transthyretin (<i>TTR</i>) gene. The prevalence of hATTR is still unclear and likely underestimated in many countries. In order to apply new therapies in a targeted manner, ... Read more >>

J Clin Med (Journal of clinical medicine)
[2020, 9(7):]

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The autophagic marker p62 highlights Alzheimer type II astrocytes in metabolic/hepatic encephalopathy.

Ellen Gelpi, Jasmin Rahimi, Sigrid Klotz, Susanne Schmid, Gerda Ricken, Sara Forcen-Vega, Herbert Budka, Gabor G Kovacs,

Metabolic/hepatic encephalopathy is neuropathologically characterized by the presence of Alzheimer type II astrocytes (AA II) with large and clear nuclear morphology. To date, there is no good immunohistochemical marker to better identify these cells. Here, we assessed cases of hepatic encephalopathy of different etiologies by immunohistochemistry using an anti-p62 antibody. ... Read more >>

Neuropathology (Neuropathology : official journal of the Japanese Society of Neuropathology)
[2020, 40(4):358-366]

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Distribution patterns of tau pathology in progressive supranuclear palsy.

Gabor G Kovacs, Milica Jecmenica Lukic, David J Irwin, Thomas Arzberger, Gesine Respondek, Edward B Lee, David Coughlin, Armin Giese, Murray Grossman, Carolin Kurz, Corey T McMillan, Ellen Gelpi, Yaroslau Compta, John C van Swieten, Laura Donker Laat, Claire Troakes, Safa Al-Sarraj, John L Robinson, Sigrun Roeber, Sharon X Xie, Virginia M-Y Lee, John Q Trojanowski, Günter U Höglinger,

Progressive supranuclear palsy (PSP) is a 4R-tauopathy predominated by subcortical pathology in neurons, astrocytes, and oligodendroglia associated with various clinical phenotypes. In the present international study, we addressed the question of whether or not sequential distribution patterns can be recognized for PSP pathology. We evaluated heat maps and distribution patterns ... Read more >>

Acta Neuropathol (Acta neuropathologica)
[2020, 140(2):99-119]

Cited: 4 times

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Mitochondrial respiratory chain deficiency correlates with the severity of neuropathology in sporadic Creutzfeldt-Jakob disease.

Irene H Flønes, Gerda Ricken, Sigrid Klotz, Alexandra Lang, Thomas Ströbel, Christian Dölle, Gabor G Kovacs, Charalampos Tzoulis,

Mitochondrial dysfunction has been implicated in multiple neurodegenerative diseases but remains largely unexplored in Creutzfeldt-Jakob disease. Here, we characterize the mitochondrial respiratory chain at the individual neuron level in the MM1 and VV2 common molecular subtypes of sporadic Creutzfeldt-Jakob disease. Moreover, we investigate the associations between the mitochondrial respiratory chain ... Read more >>

Acta Neuropathol Commun (Acta neuropathologica communications)
[2020, 8(1):50]

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Astroglia and Tau: New Perspectives.

Gabor G Kovacs,

Astrocytes contribute to the pathogenesis of neurodegenerative proteinopathies as influencing neuronal degeneration or neuroprotection, and also act as potential mediators of the propagation or elimination of disease-associated proteins. Protein astrogliopathies can be observed in different forms of neurodegenerative conditions. Morphological characterization of astrogliopathy is used only for the classification of ... Read more >>

Front Aging Neurosci (Frontiers in aging neuroscience)
[2020, 12:96]

Cited: 5 times

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Proteomics-Enriched Prediction Model for Poor Neurologic Outcome in Cardiac Arrest Survivors.

Klaus Distelmaier, Besnik Muqaku, Raphael Wurm, Henrike Arfsten, Stefan Seidel, Gabor G Kovacs, Rupert L Mayer, Thomas Szekeres, Christine Wallisch, Pia Hubner, Georg Goliasch, Georg Heinze, Gottfried Heinz, Fritz Sterz, Christopher Gerner, Christopher Adlbrecht,

OBJECTIVES:Neurologic outcome prediction in out-of-hospital cardiac arrest survivors is highly limited due to the lack of consistent predictors of clinically relevant brain damage. The present study aimed to identify novel biomarkers of neurologic recovery to improve early prediction of neurologic outcome. DESIGN:Prospective, single-center study, SETTING:: University-affiliated tertiary care center. PATIENTS:We ... Read more >>

Crit Care Med (Critical care medicine)
[2020, 48(2):167-175]

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Diagnostic Accuracy of Prion Disease Biomarkers in Iatrogenic Creutzfeldt-Jakob Disease.

Franc Llorens, Anna Villar-Piqué, Peter Hermann, Matthias Schmitz, Olga Calero, Christiane Stehmann, Shannon Sarros, Fabio Moda, Isidre Ferrer, Anna Poleggi, Maurizio Pocchiari, Marcella Catania, Sigrid Klotz, Carl O'Regan, Francesca Brett, Josephine Heffernan, Anna Ladogana, Steven J Collins, Miguel Calero, Gabor G Kovacs, Inga Zerr,

Human prion diseases are classified into sporadic, genetic, and acquired forms. Within this last group, iatrogenic Creutzfeldt-Jakob disease (iCJD) is caused by human-to-human transmission through surgical and medical procedures. After reaching an incidence peak in the 1990s, it is believed that the iCJD historical period is probably coming to an ... Read more >>

Biomolecules (Biomolecules)
[2020, 10(2):]

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CpG and non-CpG Presenilin1 methylation pattern in course of neurodevelopment and neurodegeneration is associated with gene expression in human and murine brain.

Noemi Monti, Rosaria A Cavallaro, Andrea Stoccoro, Vincenzina Nicolia, Sigfrido Scarpa, Gabor G Kovacs, Maria Teresa Fiorenza, Marco Lucarelli, Eleonora Aronica, Isidre Ferrer, Fabio Coppedè, Aron M Troen, Andrea Fuso,

The Presenilin1 (<i>PSEN1</i>) gene encodes the catalytic peptide of the γ-secretase complex, a key enzyme that cleaves the amyloid-β protein precursor (AβPP), to generate the amyloid-β (Aβ) peptides, involved in Alzheimer's Disease (AD). Other substrates of the γ-secretase, such as E-cadherin and Notch1, are involved in neurodevelopment and haematopoiesis. Gene-specific ... Read more >>

Epigenetics (Epigenetics)
[2020, 15(8):781-799]

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Fulminant corticobasal degeneration: a distinct variant with predominant neuronal tau aggregates.

Helen Ling, Ellen Gelpi, Karen Davey, Zane Jaunmuktane, Kin Y Mok, Edwin Jabbari, Roberto Simone, Lea R'Bibo, Sebastian Brandner, Matthew J Ellis, Johannes Attems, David Mann, Glenda M Halliday, S Al-Sarraj, J Hedreen, James W Ironside, Gabor G Kovacs, E Kovari, S Love, Jean Paul G Vonsattel, Kieren S J Allinson, Daniela Hansen, Teisha Bradshaw, Núria Setó-Salvia, Selina Wray, Rohan de Silva, Huw R Morris, Thomas T Warner, John Hardy, Janice L Holton, Tamas Revesz,

Corticobasal degeneration typically progresses gradually over 5-7 years from onset till death. Fulminant corticobasal degeneration cases with a rapidly progressive course were rarely reported (RP-CBD). This study aimed to investigate their neuropathological characteristics. Of the 124 autopsy-confirmed corticobasal degeneration cases collected from 14 centres, we identified 6 RP-CBD cases (4.8%) who ... Read more >>

Acta Neuropathol (Acta neuropathologica)
[2020, 139(4):717-734]

Cited: 2 times

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Brain-wide genetic mapping identifies the indusium griseum as a prenatal target of pharmacologically unrelated psychostimulants.

Janos Fuzik, Sabah Rehman, Fatima Girach, Andras G Miklosi, Solomiia Korchynska, Gloria Arque, Roman A Romanov, János Hanics, Ludwig Wagner, Konstantinos Meletis, Yuchio Yanagawa, Gabor G Kovacs, Alán Alpár, Tomas G M Hökfelt, Tibor Harkany,

Psychostimulant use is an ever-increasing socioeconomic burden, including a dramatic rise during pregnancy. Nevertheless, brain-wide effects of psychostimulant exposure are incompletely understood. Here, we performed Fos-CreER<sup>T2</sup>-based activity mapping, correlated for pregnant mouse dams and their fetuses with amphetamine, nicotine, and caffeine applied acutely during midgestation. While light-sheet microscopy-assisted intact tissue ... Read more >>

Proc Natl Acad Sci U S A (Proceedings of the National Academy of Sciences of the United States of America)
[2019, 116(51):25958-25967]

Cited: 2 times

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Globular Glial Tauopathy Type I Presenting as Atypical Progressive Aphasia, With Comorbid Limbic-Predominant Age-Related TDP-43 Encephalopathy.

Robert Rusina, Zsolt Csefalvay, Gabor G Kovacs, Jiri Keller, Alena Javurkova, Radoslav Matej,

Globular glial tauopathies (GGTs) have heterogeneous presentations with little available information regarding typical clinical manifestations. We report on a case of atypical primary progressive aphasia (PPA) due to comorbid GGT and limbic transactive response DNA binding protein of 43 kDa (TDP-43) proteinopathy. The initial clinical phenotype was compatible with the ... Read more >>

Front Aging Neurosci (Frontiers in aging neuroscience)
[2019, 11:336]

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Evaluation of Human Cerebrospinal Fluid Malate Dehydrogenase 1 as a Marker in Genetic Prion Disease Patients.

Inga Zerr, Anna Villar-Piqué, Vanda Edit Schmitz, Anna Poleggi, Maurizio Pocchiari, Raquel Sánchez-Valle, Miguel Calero, Olga Calero, Inês Baldeiras, Isabel Santana, Gabor G Kovacs, Franc Llorens, Matthias Schmitz,

The exploration of accurate diagnostic markers for differential diagnosis of neurodegenerative diseases is an ongoing topic. A previous study on cerebrospinal fluid (CSF)-mitochondrial malate dehydrogenase 1 (MDH1) in sporadic Creutzfeldt-Jakob disease (sCJD) patients revealed a highly significant upregulation of MDH1. Here, we measured the CSF levels of MDH1 via enzyme-linked ... Read more >>

Biomolecules (Biomolecules)
[2019, 9(12):]

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Corticobasal degeneration.

Gerard M Saranza, Jennifer L Whitwell, Gabor G Kovacs, Anthony E Lang,

Corticobasal degeneration (CBD) is a rare neurodegenerative disease characterized by the predominance of pathological 4 repeat tau deposition in various cell types and anatomical regions. Corticobasal syndrome (CBS) is one of the clinical phenotypes associated with CBD pathology, manifesting as a progressive asymmetric akinetic-rigid, poorly levodopa-responsive parkinsonism, with cerebral cortical ... Read more >>

Int Rev Neurobiol (International review of neurobiology)
[2019, 149:87-136]

Cited: 2 times

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