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Acta Neuropathologica

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https://www.readbyqxmd.com/read/29663066/infectious-prions-do-not-induce-a%C3%AE-deposition-in-an-in-vivo-seeding-model
#1
LETTER
Jay Rasmussen, Susanne Krasemann, Hermann Altmeppen, Petra Schwarz, Juliane Schelle, Adriano Aguzzi, Markus Glatzel, Mathias Jucker
No abstract text is available yet for this article.
April 16, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29644394/genomic-analysis-reveals-secondary-glioblastoma-after-radiotherapy-in-a-subset-of-recurrent-medulloblastomas
#2
Ji Hoon Phi, Ae Kyung Park, Semin Lee, Seung Ah Choi, In-Pyo Baek, Pora Kim, Eun-Hye Kim, Hee Chul Park, Byung Chul Kim, Jong Bhak, Sung-Hye Park, Ji Yeoun Lee, Kyu-Chang Wang, Dong-Seok Kim, Kyu Won Shim, Se Hoon Kim, Chae-Yong Kim, Seung-Ki Kim
Despite great advances in understanding of molecular pathogenesis and achievement of a high cure rate in medulloblastoma, recurrent medulloblastomas are still dismal. Additionally, misidentification of secondary malignancies due to histological ambiguity leads to misdiagnosis and eventually to inappropriate treatment. Nevertheless, the genomic characteristics of recurrent medulloblastomas are poorly understood, largely due to a lack of matched primary and recurrent tumor tissues. We performed a genomic analysis of recurrent tumors from 17 pediatric medulloblastoma patients...
April 11, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29627952/loss-of-histone-h3k27me3-identifies-a-subset-of-meningiomas-with-increased-risk-of-recurrence
#3
Leah M Katz, Thomas Hielscher, Benjamin Liechty, Joshua Silverman, David Zagzag, Rajeev Sen, Peter Wu, John G Golfinos, David Reuss, Marian Christoph Neidert, Hans-Georg Wirsching, Peter Baumgarten, Christel Herold-Mende, Wolfgang Wick, Patrick N Harter, Michael Weller, Andreas von Deimling, Matija Snuderl, Chandra Sen, Felix Sahm
Epigenetic patterns on the level of DNA methylation have already been shown to separate clinically relevant subgroups of meningiomas. We here set out to identify potential prognostic implications of epigenetic modification on the level of histones with focus on H3K27 trimethylation (H3K27me3). H3K27me3 was assessed by immunohistochemistry on 232 meningiomas from 232 patients. In 194 cases, trimethylation was detected in tumor cells. In 25 cases, staining was limited to vessels while all tumor cells were negative...
April 7, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29616301/reconstructing-the-molecular-life-history-of-gliomas
#4
REVIEW
Floris P Barthel, Pieter Wesseling, Roel G W Verhaak
At the time of their clinical manifestation, the heterogeneous group of adult and pediatric gliomas carries a wide range of diverse somatic genomic alterations, ranging from somatic single-nucleotide variants to structural chromosomal rearrangements. Somatic abnormalities may have functional consequences, such as a decrease, increase or change in mRNA transcripts, and cells pay a penalty for maintaining them. These abnormalities, therefore, must provide cells with a competitive advantage to become engrained into the glioma genome...
April 3, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29600398/mutations-in-lrrk2-amplify-cell-to-cell-protein-aggregate-propagation-a-hypothesis
#5
LETTER
Patrick A Lewis
No abstract text is available yet for this article.
March 29, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29589097/an-intronic-vntr-affects-splicing-of-abca7-and-increases-risk-of-alzheimer-s-disease
#6
Arne De Roeck, Lena Duchateau, Jasper Van Dongen, Rita Cacace, Maria Bjerke, Tobi Van den Bossche, Patrick Cras, Rik Vandenberghe, Peter P De Deyn, Sebastiaan Engelborghs, Christine Van Broeckhoven, Kristel Sleegers
Mutations leading to premature termination codons in ATP-Binding Cassette Subfamily A Member 7 (ABCA7) are high penetrant risk factors of Alzheimer's disease (AD). The influence of other genetic variants in ABCA7 and downstream functional mechanisms, however, is poorly understood. To address this knowledge gap, we investigated tandem repetitive regions in ABCA7 in a Belgian cohort of 1529 AD patients and control individuals and identified an intronic variable number tandem repeat (VNTR). We observed strong association between VNTR length and a genome-wide associated signal for AD in the ABCA7 locus...
March 27, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29574591/capillary-cerebral-amyloid-angiopathy-in-alzheimer-s-disease-association-with-allocortical-hippocampal-microinfarcts-and-cognitive-decline
#7
Moritz Hecht, Lara Maria Krämer, Christine A F von Arnim, Markus Otto, Dietmar Rudolf Thal
Cerebral amyloid angiopathy (CAA) is caused by the deposition of the amyloid β-protein (Aβ) in the wall of cerebral and leptomeningeal blood vessels and is related to Alzheimer's disease (AD). Capillary Aβ deposition is observed in a subset of CAA cases and represents a distinct type of CAA named capillary CAA or CAA type 1. This type of CAA is strongly associated with the presence of the apolipoprotein E ε4 allele. CAA type 1-associated AD cases often exhibit a more severe Aβ plaque pathology but less widespread neurofibrillary tangle (NFT) pathology...
March 24, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29569031/molecular-characterization-of-medulloblastomas-with-extensive-nodularity-mben
#8
Andrey Korshunov, Felix Sahm, Damian Stichel, Daniel Schrimpf, Marina Ryzhova, Olga Zheludkova, Andrey Golanov, Peter Lichter, David T W Jones, Andreas von Deimling, Stefan M Pfister, Marcel Kool
Medulloblastoma with extensive nodularity (MBEN) is a rare histological variant of medulloblastoma (MB). These tumors are usually occurring in the first 3 years of life and are associated with good prognosis. Molecular analyses of MBEN, mostly limited to single cases or small series, have shown that they always classify as sonic hedgehog (SHH)-driven MB. Here, we have analyzed 25 MBEN through genome-wide DNA methylation, copy-number profiling and targeted next-generation sequencing. Results of these analyses were compared with molecular profiles of other SHH MB histological variants...
March 22, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29564591/anaplastic-astrocytoma-with-piloid-features-a-novel-molecular-class-of-idh-wildtype-glioma-with-recurrent-mapk-pathway-cdkn2a-b-and-atrx-alterations
#9
Annekathrin Reinhardt, Damian Stichel, Daniel Schrimpf, Felix Sahm, Andrey Korshunov, David E Reuss, Christian Koelsche, Kristin Huang, Annika K Wefers, Volker Hovestadt, Martin Sill, Dorothee Gramatzki, Joerg Felsberg, Guido Reifenberger, Arend Koch, Ulrich-W Thomale, Albert Becker, Volkmar H Hans, Marco Prinz, Ori Staszewski, Till Acker, Hildegard Dohmen, Christian Hartmann, Wolf Mueller, Muin S A Tuffaha, Werner Paulus, Katharina Heß, Benjamin Brokinkel, Jens Schittenhelm, Camelia-Maria Monoranu, Almuth Friederike Kessler, Mario Loehr, Rolf Buslei, Martina Deckert, Christian Mawrin, Patricia Kohlhof, Ekkehard Hewer, Adriana Olar, Fausto J Rodriguez, Caterina Giannini, Amulya A NageswaraRao, Uri Tabori, Nuno Miguel Nunes, Michael Weller, Ute Pohl, Zane Jaunmuktane, Sebastian Brandner, Andreas Unterberg, Daniel Hänggi, Michael Platten, Stefan M Pfister, Wolfgang Wick, Christel Herold-Mende, David T W Jones, Andreas von Deimling, David Capper
Tumors with histological features of pilocytic astrocytoma (PA), but with increased mitotic activity and additional high-grade features (particularly microvascular proliferation and palisading necrosis) have often been designated anaplastic pilocytic astrocytomas. The status of these tumors as a separate entity has not yet been conclusively demonstrated and molecular features have only been partially characterized. We performed DNA methylation profiling of 102 histologically defined anaplastic pilocytic astrocytomas...
March 21, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29557506/the-natural-hla-ligandome-of-glioblastoma-stem-like-cells-antigen-discovery-for-t-cell-based-immunotherapy
#10
Marian Christoph Neidert, Daniel Johannes Kowalewski, Manuela Silginer, Konstantina Kapolou, Linus Backert, Lena Katharina Freudenmann, Janet Kerstin Peper, Ana Marcu, Sophie Shih-Yüng Wang, Juliane Sarah Walz, Fabian Wolpert, Hans-Georg Rammensee, Reinhard Henschler, Katrin Lamszus, Manfred Westphal, Patrick Roth, Luca Regli, Stefan Stevanović, Michael Weller, Günter Eisele
Glioblastoma is the most frequent malignant primary brain tumor. In a hierarchical tumor model, glioblastoma stem-like cells (GSC) play a major role in tumor initiation and maintenance as well as in therapy resistance and recurrence. Thus, targeting this cellular subset may be key to effective immunotherapy. Here, we present a mass spectrometry-based analysis of HLA-presented peptidomes of GSC and glioblastoma patient specimens. Based on the analysis of patient samples (n = 9) and GSC (n = 3), we performed comparative HLA peptidome profiling against a dataset of normal human tissues...
March 20, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29549424/energy-metabolism-in-als-an-underappreciated-opportunity
#11
REVIEW
Tijs Vandoorne, Katrien De Bock, Ludo Van Den Bosch
Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive and fatal neurodegenerative disorder that primarily affects motor neurons. Despite our increased understanding of the genetic factors contributing to ALS, no effective treatment is available. A growing body of evidence shows disturbances in energy metabolism in ALS. Moreover, the remarkable vulnerability of motor neurons to ATP depletion has become increasingly clear. Here, we review metabolic alterations present in ALS patients and models, discuss the selective vulnerability of motor neurons to energetic stress, and provide an overview of tested and emerging metabolic approaches to treat ALS...
March 16, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29541918/tumour-compartment-transcriptomics-demonstrates-the-activation-of-inflammatory-and-odontogenic-programmes-in-human-adamantinomatous-craniopharyngioma-and-identifies-the-mapk-erk-pathway-as-a-novel-therapeutic-target
#12
John R Apps, Gabriela Carreno, Jose Mario Gonzalez-Meljem, Scott Haston, Romain Guiho, Julie E Cooper, Saba Manshaei, Nital Jani, Annett Hölsken, Benedetta Pettorini, Robert J Beynon, Deborah M Simpson, Helen C Fraser, Ying Hong, Shirleen Hallang, Thomas J Stone, Alex Virasami, Andrew M Donson, David Jones, Kristian Aquilina, Helen Spoudeas, Abhijit R Joshi, Richard Grundy, Lisa C D Storer, Márta Korbonits, David A Hilton, Kyoko Tossell, Selvam Thavaraj, Mark A Ungless, Jesus Gil, Rolf Buslei, Todd Hankinson, Darren Hargrave, Colin Goding, Cynthia L Andoniadou, Paul Brogan, Thomas S Jacques, Hywel J Williams, Juan Pedro Martinez-Barbera
Adamantinomatous craniopharyngiomas (ACPs) are clinically challenging tumours, the majority of which have activating mutations in CTNNB1. They are histologically complex, showing cystic and solid components, the latter comprised of different morphological cell types (e.g. β-catenin-accumulating cluster cells and palisading epithelium), surrounded by a florid glial reaction with immune cells. Here, we have carried out RNA sequencing on 18 ACP samples and integrated these data with an existing ACP transcriptomic dataset...
March 14, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29541917/aberrant-cerebellar-purkinje-cell-function-repaired-in-vivo-by-fusion-with-infiltrating-bone-marrow-derived-cells
#13
Kevin C Kemp, Rimi Dey, Johan Verhagen, Neil J Scolding, Maria M Usowicz, Alastair Wilkins
Bone marrow-derived cells are known to infiltrate the adult brain and fuse with cerebellar Purkinje cells. Histological observations that such heterotypic cell fusion events are substantially more frequent following cerebellar injury suggest they could have a role in the protection of mature brain neurons. To date, the possibility that cell fusion can preserve or restore the structure and function of adult brain neurons has not been directly addressed; indeed, though frequently suggested, the possibility of benefit has always been rather speculative...
March 14, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29536165/interaction-of-amyloidogenic-proteins-in-pancreatic-%C3%AE-cells-from-subjects-with-synucleinopathies
#14
Ivan Martinez-Valbuena, Irene Amat-Villegas, Rafael Valenti-Azcarate, Maria Del Mar Carmona-Abellan, Irene Marcilla, Maria-Teresa Tuñon, Maria-Rosario Luquin
Parkinson's disease patients experience a wide range of non-motor symptoms that may be provoked by deposits of phosphorylated α-synuclein in the peripheral nervous system. Pre-existing diabetes mellitus might be a risk factor for developing Parkinson's disease, and indeed, nearly 60% of Parkinson's disease patients are insulin resistant. Thus, we have investigated whether phosphorylated α-synuclein is deposited in pancreatic tissue of subjects with synucleinopathies. We studied pancreatic tissue from 39 subjects diagnosed with Parkinson's disease, Lewy body Dementia or incidental Lewy bodies disease, as well as that from 34 subjects with diabetes mellitus and a normal neuropathological examination, and 52 subjects with a normal neuropathological examination...
March 13, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29511858/the-referee-who-agrees-to-review-and-never-responds-again-nero-a-series-of-37-cases-of-an-emerging-entity
#15
EDITORIAL
Werner Paulus
No abstract text is available yet for this article.
March 6, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29508058/fatal-a%C3%AE-cerebral-amyloid-angiopathy-4-decades-after-a-dural-graft-at-the-age-of-2-years
#16
LETTER
Dominique Hervé, Maximilien Porché, Lucie Cabrejo, Céline Guidoux, Elisabeth Tournier-Lasserve, Gaël Nicolas, Homa Adle-Biassette, Isabelle Plu, Hugues Chabriat, Charles Duyckaerts
No abstract text is available yet for this article.
March 5, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29502201/integrated-neurodegenerative-disease-autopsy-diagnosis
#17
LETTER
Edward B Lee
No abstract text is available yet for this article.
March 3, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29502200/differential-%C3%AE-synuclein-expression-contributes-to-selective-vulnerability-of-hippocampal-neuron-subpopulations-to-fibril-induced-toxicity
#18
Esteban Luna, Samantha C Decker, Dawn M Riddle, Anna Caputo, Bin Zhang, Tracy Cole, Carrie Caswell, Sharon X Xie, Virginia M Y Lee, Kelvin C Luk
The accumulation of misfolded α-synuclein (aSyn) and neuron loss define several neurodegenerative disorders including Parkinson's disease (PD) and dementia with Lewy bodies (DLB). However, the precise relationship between pathology and neurotoxicity and why these processes disproportionately affect certain neuron subpopulations are poorly understood. We show here that Math2-expressing neurons in the hippocampal Cornu ammonis (CA), a region significantly affected by aSyn pathology in advanced PD and DLB, are highly susceptible to pathological seeding with pre-formed fibrils (PFFs), in contrast to dentate gyrus neurons, which are relatively spared...
March 3, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29497819/cimpact-now-update-2-diagnostic-clarifications-for-diffuse-midline-glioma-h3-k27m-mutant-and-diffuse-astrocytoma-anaplastic-astrocytoma-idh-mutant
#19
LETTER
David N Louis, Caterina Giannini, David Capper, Werner Paulus, Dominique Figarella-Branger, M Beatriz Lopes, Tracy T Batchelor, J Gregory Cairncross, Martin van den Bent, Wolfgang Wick, Pieter Wesseling
No abstract text is available yet for this article.
March 1, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29460007/diffuse-gliomas-classified-by-1p-19q-co-deletion-tert-promoter-and-idh-mutation-status-are-associated-with-specific-genetic-risk-loci
#20
Karim Labreche, Ben Kinnersley, Giulia Berzero, Anna Luisa Di Stefano, Amithys Rahimian, Ines Detrait, Yannick Marie, Benjamin Grenier-Boley, Khe Hoang-Xuan, Jean-Yves Delattre, Ahmed Idbaih, Richard S Houlston, Marc Sanson
Recent genome-wide association studies of glioma have led to the discovery of single nucleotide polymorphisms (SNPs) at 25 loci influencing risk. Gliomas are heterogeneous, hence to investigate the relationship between risk SNPs and glioma subtype we analysed 1659 tumours profiled for IDH mutation, TERT promoter mutation and 1p/19q co-deletion. These data allowed definition of five molecular subgroups of glioma: triple-positive (IDH mutated, 1p/19q co-deletion, TERT promoter mutated); TERT-IDH (IDH mutated, TERT promoter mutated, 1p/19q-wild-type); IDH-only (IDH mutated, 1p/19q wild-type, TERT promoter wild-type); triple-negative (IDH wild-type, 1p/19q wild-type, TERT promoter wild-type) and TERT-only (TERT promoter mutated, IDH wild-type, 1p/19q wild-type)...
February 19, 2018: Acta Neuropathologica
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