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Acta Neuropathologica

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https://www.readbyqxmd.com/read/27909809/announcing-cimpact-now-the-consortium-to-inform-molecular-and-practical-approaches-to-cns-tumor-taxonomy
#1
EDITORIAL
David N Louis, Ken Aldape, Daniel J Brat, David Capper, David W Ellison, Cynthia Hawkins, Werner Paulus, Arie Perry, Guido Reifenberger, Dominique Figarella-Branger, Pieter Wesseling, Tracy T Batchelor, J Gregory Cairncross, Stefan M Pfister, Stefan Rutkowski, Michael Weller, Wolfgang Wick, Andreas von Deimling
No abstract text is available yet for this article.
December 1, 2016: Acta Neuropathologica
https://www.readbyqxmd.com/read/27900460/tau-neuropathology-correlates-with-fdg-pet-but-not-av-1451-pet-in-progressive-supranuclear-palsy
#2
LETTER
Ruben Smith, Michael Schöll, Michael Honer, Christer F Nilsson, Elisabet Englund, Oskar Hansson
No abstract text is available yet for this article.
November 29, 2016: Acta Neuropathologica
https://www.readbyqxmd.com/read/27896434/towards-a-functional-pathology-of-hereditary-neuropathies
#3
REVIEW
Joachim Weis, Kristl G Claeys, Andreas Roos, Hamid Azzedine, Istvan Katona, J Michael Schröder, Jan Senderek
A growing number of hereditary neuropathies have been assigned to causative gene defects in recent years. The study of human nerve biopsy samples has contributed substantially to the discovery of many of these neuropathy genes. Genotype-phenotype correlations based on peripheral nerve pathology have provided a comprehensive picture of the consequences of these mutations. Intriguingly, several gene defects lead to distinguishable lesion patterns that can be studied in nerve biopsies. These characteristic features include the loss of certain nerve fiber populations and a large spectrum of distinct structural changes of axons, Schwann cells and other components of peripheral nerves...
November 28, 2016: Acta Neuropathologica
https://www.readbyqxmd.com/read/27888296/toll-like-receptor-2-is-increased-in-neurons-in-parkinson-s-disease-brain-and-may-contribute-to-alpha-synuclein-pathology
#4
Nicolas Dzamko, Amanda Gysbers, Gayathri Perera, Anita Bahar, Amrita Shankar, Jianqun Gao, YuHong Fu, Glenda M Halliday
Inflammation is likely a key contributor to the pathogenesis of Parkinson's disease (PD), a progressively debilitating neurodegenerative disease that is accompanied by a pathological accumulation of the α-synuclein protein in a staged manner through the brain. What leads to the accumulation of α-synuclein in PD and how this relates to inflammatory pathways, however, is not entirely clear. Toll-like receptor (TLR) signaling is a major pathway mediating inflammation and, in particular, TLR2 is increasingly being implicated in PD...
November 25, 2016: Acta Neuropathologica
https://www.readbyqxmd.com/read/27885490/localized-cortical-chronic-traumatic-encephalopathy-pathology-after-single-severe-axonal-injury-in-human-brain
#5
Sharon B Shively, Sarah L Edgerton, Diego Iacono, Dushyant P Purohit, Bao-Xi Qu, Vahram Haroutunian, Kenneth L Davis, Ramon Diaz-Arrastia, Daniel P Perl
Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repetitive mild impact traumatic brain injury from contact sports. Recently, a consensus panel defined the pathognomonic lesion for CTE as accumulations of abnormally hyperphosphorylated tau (p-tau) in neurons (neurofibrillary tangles), astrocytes and cell processes distributed around small blood vessels at sulcal depths in irregular patterns within the cortex. The pathophysiological mechanism for this lesion is unknown. Moreover, a subset of CTE cases harbors cortical β-amyloid plaques...
November 24, 2016: Acta Neuropathologica
https://www.readbyqxmd.com/read/27878366/widespread-tau-seeding-activity-at-early-braak-stages
#6
Jennifer L Furman, Jaime Vaquer-Alicea, Charles L White, Nigel J Cairns, Peter T Nelson, Marc I Diamond
Transcellular propagation of tau aggregates may underlie the progression of pathology in Alzheimer's disease (AD) and other tauopathies. Braak staging (B1, B2, B3) is based on phospho-tau accumulation within connected brain regions: entorhinal cortex (B1); hippocampus/limbic system (B2); and frontal and parietal lobes (B3). We previously developed a specific and sensitive assay that uses flow cytometry to quantify tissue seeding activity based on fluorescence resonance energy transfer (FRET) in cells that stably express tau reporter proteins...
November 22, 2016: Acta Neuropathologica
https://www.readbyqxmd.com/read/27866231/presynaptic-proteins-complexin-i-and-complexin-ii-differentially-influence-cognitive-function-in-early-and-late-stages-of-alzheimer-s-disease
#7
Alfredo Ramos-Miguel, Ken Sawada, Andrea A Jones, Allen E Thornton, Alasdair M Barr, Sue E Leurgans, Julie A Schneider, David A Bennett, William G Honer
Progressive accumulation of Alzheimer's disease-related pathology is associated with cognitive dysfunction. Differences in cognitive reserve may contribute to individual differences in cognitive function in the presence of comparable neuropathology. The protective effects of cognitive reserve could contribute differentially in early versus late stages of the disease. We investigated presynaptic proteins as measures of brain reserve (a subset of total cognitive reserve), and used Braak staging to estimate the progression of Alzheimer's disease...
November 19, 2016: Acta Neuropathologica
https://www.readbyqxmd.com/read/27858204/the-current-consensus-on-the-clinical-management-of-intracranial-ependymoma-and-its-distinct-molecular-variants
#8
Kristian W Pajtler, Stephen C Mack, Vijay Ramaswamy, Christian A Smith, Hendrik Witt, Amy Smith, Jordan R Hansford, Katja von Hoff, Karen D Wright, Eugene Hwang, Didier Frappaz, Yonehiro Kanemura, Maura Massimino, Cécile Faure-Conter, Piergiorgio Modena, Uri Tabori, Katherine E Warren, Eric C Holland, Koichi Ichimura, Felice Giangaspero, David Castel, Andreas von Deimling, Marcel Kool, Peter B Dirks, Richard G Grundy, Nicholas K Foreman, Amar Gajjar, Andrey Korshunov, Jonathan Finlay, Richard J Gilbertson, David W Ellison, Kenneth D Aldape, Thomas E Merchant, Eric Bouffet, Stefan M Pfister, Michael D Taylor
Multiple independent genomic profiling efforts have recently identified clinically and molecularly distinct subgroups of ependymoma arising from all three anatomic compartments of the central nervous system (supratentorial brain, posterior fossa, and spinal cord). These advances motivated a consensus meeting to discuss: (1) the utility of current histologic grading criteria, (2) the integration of molecular-based stratification schemes in future clinical trials for patients with ependymoma and (3) current therapy in the context of molecular subgroups...
November 17, 2016: Acta Neuropathologica
https://www.readbyqxmd.com/read/27817117/differences-in-t-cell-cytotoxicity-and-cell-death-mechanisms-between-progressive-multifocal-leukoencephalopathy-herpes-simplex-virus-encephalitis-and-cytomegalovirus-encephalitis
#9
Susanne Laukoter, Helmut Rauschka, Anna R Tröscher, Ulrike Köck, Etsuji Saji, Kurt Jellinger, Hans Lassmann, Jan Bauer
During the appearance of human immunodeficiency virus infection in the 1980 and the 1990s, progressive multifocal leukoencephalopathy (PML), a viral encephalitis induced by the JC virus, was the leading opportunistic brain infection. As a result of the use of modern immunomodulatory compounds such as Natalizumab and Rituximab, the number of patients with PML is once again increasing. Despite the presence of PML over decades, little is known regarding the mechanisms leading to death of infected cells and the role the immune system plays in this process...
November 5, 2016: Acta Neuropathologica
https://www.readbyqxmd.com/read/27812793/uk-iatrogenic-creutzfeldt-jakob-disease-investigating-human-prion-transmission-across-genotypic-barriers-using-human-tissue-based-and-molecular-approaches
#10
Diane L Ritchie, Marcelo A Barria, Alexander H Peden, Helen M Yull, James Kirkpatrick, Peter Adlard, James W Ironside, Mark W Head
Creutzfeldt-Jakob disease (CJD) is the prototypic human prion disease that occurs most commonly in sporadic and genetic forms, but it is also transmissible and can be acquired through medical procedures, resulting in iatrogenic CJD (iCJD). The largest numbers of iCJD cases that have occurred worldwide have resulted from contaminated cadaveric pituitary-derived human growth hormone (hGH) and its use to treat primary and secondary growth hormone deficiency. We report a comprehensive, tissue-based and molecular genetic analysis of the largest series of UK hGH-iCJD cases reported to date, including in vitro kinetic molecular modelling of genotypic factors influencing prion transmission...
November 3, 2016: Acta Neuropathologica
https://www.readbyqxmd.com/read/27812792/polymorphous-low-grade-neuroepithelial-tumor-of-the-young-plnty-an-epileptogenic-neoplasm-with-oligodendroglioma-like-components-aberrant-cd34-expression-and-genetic-alterations-involving-the-map-kinase-pathway
#11
Jason T Huse, Matija Snuderl, David T W Jones, Carole D Brathwaite, Nolan Altman, Ehud Lavi, Richard Saffery, Alexandra Sexton-Oates, Ingmar Blumcke, David Capper, Matthias A Karajannis, Ryma Benayed, Lukas Chavez, Cheddhi Thomas, Jonathan Serrano, Laetitia Borsu, Marc Ladanyi, Marc K Rosenblum
Epileptogenic tumors affecting children and young adults are a morphologically diverse collection of neuroepithelial neoplasms that, as a group, exhibit varying levels of glial and/or neuronal differentiation. Recent advances in molecular profiling technology, including comprehensive DNA sequencing and methylation analysis, have enabled the application of more precise and biologically relevant classification schemes to these tumors. In this report, we describe a morphologically and molecularly distinct epileptogenic neoplasm, the polymorphous low-grade neuroepithelial tumor of the young (PLNTY), which likely accounts for a sizable portion of oligodendroglioma-like tumors affecting the pediatric population...
November 3, 2016: Acta Neuropathologica
https://www.readbyqxmd.com/read/27796537/slow-expansion-of-multiple-sclerosis-iron-rim-lesions-pathology-and-7%C3%A2-t-magnetic-resonance-imaging
#12
Assunta Dal-Bianco, Günther Grabner, Claudia Kronnerwetter, Michael Weber, Romana Höftberger, Thomas Berger, Eduard Auff, Fritz Leutmezer, Siegfried Trattnig, Hans Lassmann, Francesca Bagnato, Simon Hametner
In multiple sclerosis (MS), iron accumulates inside activated microglia/macrophages at edges of some chronic demyelinated lesions, forming rims. In susceptibility-based magnetic resonance imaging at 7 T, iron-laden microglia/macrophages induce a rim of decreased signal at lesion edges and have been associated with slowly expanding lesions. We aimed to determine (1) what lesion types and stages are associated with iron accumulation at their edges, (2) what cells at the lesion edges accumulate iron and what is their activation status, (3) how reliably can iron accumulation at the lesion edge be detected by 7 T magnetic resonance imaging (MRI), and (4) if lesions with rims enlarge over time in vivo, when compared to lesions without rims...
October 27, 2016: Acta Neuropathologica
https://www.readbyqxmd.com/read/27771772/reduced-vascular-amyloid-burden-at-microhemorrhage-sites-in-cerebral-amyloid-angiopathy
#13
Susanne J van Veluw, Hugo J Kuijf, Andreas Charidimou, Anand Viswanathan, Geert Jan Biessels, Annemieke J M Rozemuller, Matthew P Frosch, Steven M Greenberg
Microhemorrhages are strongly associated with advanced cerebral amyloid angiopathy (CAA). Although it has been frequently proposed that the deposition of Aβ in the walls of cortical vessels directly causes microhemorrhages, this has not been studied in great detail, mainly because the ruptured vessels are often missed on routine histopathologic examination. Here, we examined histopathological data from studies targeting microhemorrhages with high-resolution ex vivo 7 T MRI in nine cases with moderate-to-severe CAA, and assessed the presence of Aβ in the walls of involved vessels...
October 22, 2016: Acta Neuropathologica
https://www.readbyqxmd.com/read/27770235/deep-sequencing-reveals-persistence-of-cell-associated-mumps-vaccine-virus-in-chronic-encephalitis
#14
Sofia Morfopoulou, Edward T Mee, Sarah M Connaughton, Julianne R Brown, Kimberly Gilmour, W K 'Kling' Chong, W Paul Duprex, Deborah Ferguson, Mike Hubank, Ciaran Hutchinson, Marios Kaliakatsos, Stephen McQuaid, Simon Paine, Vincent Plagnol, Christopher Ruis, Alex Virasami, Hong Zhan, Thomas S Jacques, Silke Schepelmann, Waseem Qasim, Judith Breuer
Routine childhood vaccination against measles, mumps and rubella has virtually abolished virus-related morbidity and mortality. Notwithstanding this, we describe here devastating neurological complications associated with the detection of live-attenuated mumps virus Jeryl Lynn (MuV(JL5)) in the brain of a child who had undergone successful allogeneic transplantation for severe combined immunodeficiency (SCID). This is the first confirmed report of MuV(JL5) associated with chronic encephalitis and highlights the need to exclude immunodeficient individuals from immunisation with live-attenuated vaccines...
October 21, 2016: Acta Neuropathologica
https://www.readbyqxmd.com/read/27766432/multiple-sclerosis-experimental-models-and-reality
#15
Hans Lassmann, Monika Bradl
One of the most frequent statements, provided in different variations in the introduction of experimental studies on multiple sclerosis (MS), is that "Multiple sclerosis is a demyelinating autoimmune disease and experimental autoimmune encephalomyelitis (EAE) is a suitable model to study its pathogenesis". However, so far, no single experimental model covers the entire spectrum of the clinical, pathological, or immunological features of the disease. Many different models are available, which proved to be highly useful for studying different aspects of inflammation, demyelination, remyelination, and neurodegeneration in the central nervous system...
October 20, 2016: Acta Neuropathologica
https://www.readbyqxmd.com/read/27757524/pathological-tdp-43-changes-in-betz-cells-differ-from-those-in-bulbar-and-spinal-%C3%AE-motoneurons-in-sporadic-amyotrophic-lateral-sclerosis
#16
Heiko Braak, Albert C Ludolph, Manuela Neumann, John Ravits, Kelly Del Tredici
Two nerve cells types, Betz cells in layer Vb of the primary motor neocortex and α-motoneurons of the lower brainstem and spinal cord, become involved at the beginning of the pathological cascade underlying sporadic amyotrophic lateral sclerosis (sALS). In both neuronal types, the cell nuclei forfeit their normal (non-phosphorylated) expression of the 43-kDa transactive response DNA-binding protein (TDP-43). Here, we present initial evidence that in α-motoneurons the loss of normal nuclear TDP-43 expression is followed by the formation of phosphorylated TDP-43 aggregates (pTDP-43) within the cytoplasm, whereas in Betz cells, by contrast, the loss of normal nuclear TDP-43 expression remains mostly unaccompanied by the development of cytoplasmic aggregations...
October 18, 2016: Acta Neuropathologica
https://www.readbyqxmd.com/read/27752775/eef2k-inhibition-blocks-a%C3%AE-42-neurotoxicity-by-promoting-an-nrf2-antioxidant-response
#17
Asad Jan, Brandon Jansonius, Alberto Delaidelli, Syam Prakash Somasekharan, Forum Bhanshali, Milène Vandal, Gian Luca Negri, Don Moerman, Ian MacKenzie, Frédéric Calon, Michael R Hayden, Stefan Taubert, Poul H Sorensen
Soluble oligomers of amyloid-β (Aβ) impair synaptic plasticity, perturb neuronal energy homeostasis, and are implicated in Alzheimer's disease (AD) pathogenesis. Therefore, significant efforts in AD drug discovery research aim to prevent the formation of Aβ oligomers or block their neurotoxicity. The eukaryotic elongation factor-2 kinase (eEF2K) plays a critical role in synaptic plasticity, and couples neurotransmission to local dendritic mRNA translation. Recent evidence indicates that Aβ oligomers activate neuronal eEF2K, suggesting a potential link to Aβ induced synaptic dysfunction...
October 17, 2016: Acta Neuropathologica
https://www.readbyqxmd.com/read/27730299/peripheral-vh4-%C3%A2-plasmablasts-demonstrate-autoreactive-b-cell-expansion-toward-brain-antigens-in-early-multiple-sclerosis-patients
#18
Jacqueline R Rivas, Sara J Ireland, Rati Chkheidze, William H Rounds, Joseph Lim, Jordan Johnson, Denise M O Ramirez, Ann J Ligocki, Ding Chen, Alyssa A Guzman, Mark Woodhall, Patrick C Wilson, Eric Meffre, Charles White, Benjamin M Greenberg, Patrick Waters, Lindsay G Cowell, Ann M Stowe, Nancy L Monson
Plasmablasts are a highly differentiated, antibody secreting B cell subset whose prevalence correlates with disease activity in Multiple Sclerosis (MS). For most patients experiencing partial transverse myelitis (PTM), plasmablasts are elevated in the blood at the first clinical presentation of disease (known as a clinically isolated syndrome or CIS). In this study we found that many of these peripheral plasmablasts are autoreactive and recognize primarily gray matter targets in brain tissue. These plasmablasts express antibodies that over-utilize immunoglobulin heavy chain V-region subgroup 4 (VH4) genes, and the highly mutated VH4+ plasmablast antibodies recognize intracellular antigens of neurons and astrocytes...
October 11, 2016: Acta Neuropathologica
https://www.readbyqxmd.com/read/27704282/climbing-fiber-purkinje-cell-synaptic-pathology-in-tremor-and-cerebellar-degenerative-diseases
#19
Sheng-Han Kuo, Chi-Ying Lin, Jie Wang, Peter A Sims, Ming-Kai Pan, Jyun-You Liou, Danielle Lee, William J Tate, Geoffrey C Kelly, Elan D Louis, Phyllis L Faust
Changes in climbing fiber-Purkinje cell (CF-PC) synaptic connections have been found in the essential tremor (ET) cerebellum, and these changes are correlated with tremor severity. Whether these postmortem changes are specific to ET remains to be investigated. We assessed CF-PC synaptic pathology in the postmortem cerebellum across a range of degenerative movement disorders [10 Parkinson's disease (PD) cases, 10 multiple system atrophy (MSA) cases, 10 spinocerebellar ataxia type 1 (SCA1) cases, and 20 ET cases] and 25 controls...
October 4, 2016: Acta Neuropathologica
https://www.readbyqxmd.com/read/27704281/mir-223-regulates-the-number-and-function-of-myeloid-derived-suppressor-cells-in-multiple-sclerosis-and-experimental-autoimmune-encephalomyelitis
#20
Claudia Cantoni, Francesca Cignarella, Laura Ghezzi, Bob Mikesell, Bryan Bollman, Melissa M Berrien-Elliott, Aaron R Ireland, Todd A Fehniger, Gregory F Wu, Laura Piccio
Myeloid-derived cells play important modulatory and effector roles in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells, composed of monocytic (MO) and polymorphonuclear (PMN) fractions, which can suppress T cell activities in EAE. Their role in MS remains poorly characterized. We found decreased numbers of circulating MDSCs, driven by lower frequencies of the MO-MDSCs, and higher MDSC expression of microRNA miR-223 in MS versus healthy subjects...
October 4, 2016: Acta Neuropathologica
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