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Acta Neuropathologica

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https://www.readbyqxmd.com/read/28214960/axonal-disruption-in-white-matter-underlying-cortical-sulcus-tau-pathology-in-chronic-traumatic-encephalopathy
#1
Laurena Holleran, Joong Hee Kim, Mihika Gangolli, Thor Stein, Victor Alvarez, Ann McKee, David L Brody
Chronic traumatic encephalopathy (CTE) is a progressive degenerative disorder associated with repetitive traumatic brain injury. One of the primary defining neuropathological lesions in CTE, based on the first consensus conference, is the accumulation of hyperphosphorylated tau in gray matter sulcal depths. Post-mortem CTE studies have also reported myelin loss, axonal injury and white matter degeneration. Currently, the diagnosis of CTE is restricted to post-mortem neuropathological analysis. We hypothesized that high spatial resolution advanced diffusion MRI might be useful for detecting white matter microstructural changes directly adjacent to gray matter tau pathology...
February 18, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28205010/prion-specific-and-surrogate-csf-biomarkers-in-creutzfeldt-jakob-disease-diagnostic-accuracy-in-relation-to-molecular-subtypes-and-analysis-of-neuropathological-correlates-of-p-tau-and-a%C3%AE-42-levels
#2
Francesca Lattanzio, Samir Abu-Rumeileh, Alessia Franceschini, Hideaki Kai, Giulia Amore, Ilaria Poggiolini, Marcello Rossi, Simone Baiardi, Lynne McGuire, Anna Ladogana, Maurizio Pocchiari, Alison Green, Sabina Capellari, Piero Parchi
The differential diagnosis of Creutzfeldt-Jakob disease (CJD) from other, sometimes treatable, neurological disorders is challenging, owing to the wide phenotypic heterogeneity of the disease. Real-time quaking-induced prion conversion (RT-QuIC) is a novel ultrasensitive in vitro assay, which, at variance with surrogate neurodegenerative biomarker assays, specifically targets the pathological prion protein (PrP(Sc)). In the studies conducted to date in CJD, cerebrospinal fluid (CSF) RT-QuIC showed good diagnostic sensitivity (82-96%) and virtually full specificity...
February 15, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28205009/mixed-pathologies-including-chronic-traumatic-encephalopathy-account-for-dementia-in-retired-association-football-soccer-players
#3
Helen Ling, Huw R Morris, James W Neal, Andrew J Lees, John Hardy, Janice L Holton, Tamas Revesz, David D R Williams
In retired professional association football (soccer) players with a past history of repetitive head impacts, chronic traumatic encephalopathy (CTE) is a potential neurodegenerative cause of dementia and motor impairments. From 1980 to 2010, 14 retired footballers with dementia were followed up regularly until death. Their clinical data, playing career, and concussion history were prospectively collected. Next-of-kin provided consent for six to have post-mortem brain examination. Of the 14 male participants, 13 were professional and 1 was a committed amateur...
February 15, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28184993/pathogenic-implications-of-cerebrospinal-fluid-barrier-pathology-in-neuromyelitis-optica
#4
Yong Guo, Stephen D Weigand, Bogdan F Popescu, Vanda A Lennon, Joseph E Parisi, Sean J Pittock, Natalie E Parks, Stacey L Clardy, Charles L Howe, Claudia F Lucchinetti
Pathogenic autoantibodies associated with neuromyelitis optica (NMO) induce disease by targeting aquaporin-4 (AQP4) water channels enriched on astrocytic endfeet at blood-brain interfaces. AQP4 is also expressed at cerebrospinal fluid (CSF)-brain interfaces, such as the pial glia limitans and the ependyma and at the choroid plexus blood-CSF barrier. However, little is known regarding pathology at these sites in NMO. Therefore, we evaluated AQP4 expression, microglial reactivity, and complement deposition at pial and ependymal surfaces and in the fourth ventricle choroid plexus in 23 autopsy cases with clinically and/or pathologically confirmed NMO or NMO spectrum disorder...
February 9, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28180961/dermal-phospho-alpha-synuclein-deposits-confirm-rem-sleep-behaviour-disorder-as-prodromal-parkinson-s-disease
#5
Kathrin Doppler, Hanna-Maria Jentschke, Lena Schulmeyer, David Vadasz, Annette Janzen, Markus Luster, Helmut Höffken, Geert Mayer, Joachim Brumberg, Jan Booij, Thomas Musacchio, Stephan Klebe, Elisabeth Sittig-Wiegand, Jens Volkmann, Claudia Sommer, Wolfgang H Oertel
Phosphorylated alpha-synuclein (p-alpha-syn) deposits, one of the neuropathological hallmarks of Parkinson's disease (PD), have recently been detected in dermal nerve fibres in PD patients with good specificity and sensitivity. Here, we studied whether p-alpha-syn may serve as a biomarker in patients with a high risk of developing PD, such as those with REM sleep behaviour disorder (RBD). We compared the presence and distribution of p-alpha-syn deposits in dermal nerve fibres in 18 patients with RBD, 25 patients with early PD and 20 normal controls...
February 8, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28160067/tau-aggregation-influences-cognition-and-hippocampal-atrophy-in-the-absence-of-beta-amyloid-a-clinico-imaging-pathological-study-of-primary-age-related-tauopathy-part
#6
Keith A Josephs, Melissa E Murray, Nirubol Tosakulwong, Jennifer L Whitwell, David S Knopman, Mary M Machulda, Stephen D Weigand, Bradley F Boeve, Kejal Kantarci, Leonard Petrucelli, Val J Lowe, Clifford R Jack, Ronald C Petersen, Joseph E Parisi, Dennis W Dickson
We investigate whether there is any association between the Braak neurofibrillary tangle (NFT) stage and clinical and MRI features in definite primary age-related tauopathy (PART). We analysed 52 cases with a Braak NFT tangle stage >0 and ≤IV, and a Thal phase of 0 (no beta-amyloid present). Twenty-nine (56%) were female. Median age at death was 88 years (IQR 82-92 years). Fifteen (29%) were TDP-positive (75% TDP stage I), 16 (31%) had argyrophilic grain disease and three (6%) had alpha-synuclein-positive Lewy bodies...
February 3, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28130640/expansion-of-the-classification-of-ftld-tdp-distinct-pathology-associated-with-rapidly-progressive-frontotemporal-degeneration
#7
Edward B Lee, Sílvia Porta, G Michael Baer, Yan Xu, EunRan Suh, Linda K Kwong, Lauren Elman, Murray Grossman, Virginia M-Y Lee, David J Irwin, Vivianna M Van Deerlin, John Q Trojanowski
Frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) can typically be categorized into one of four distinct histopathologic patterns of TDP-43 pathology, types A to D. The strength of this histopathologic classification lies in the association between FTLD-TDP subtypes and various clinical and genetic features of disease. Seven cases of FTLD-TDP were identified here which were difficult to classify based on existing pathologic criteria. Distinct features common to these cases included TDP-43 aggregates over a wide neuroanatomic distribution comprised of granulofilamentous neuronal inclusions, abundant grains, and oligodendroglial inclusions...
January 27, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28130639/global-epigenetic-profiling-identifies-methylation-subgroups-associated-with-recurrence-free-survival-in-meningioma
#8
Adriana Olar, Khalida M Wani, Charmaine D Wilson, Gelareh Zadeh, Franco DeMonte, David T W Jones, Stefan M Pfister, Erik P Sulman, Kenneth D Aldape
Meningioma is the most common primary brain tumor and carries a substantial risk of local recurrence. Methylation profiles of meningioma and their clinical implications are not well understood. We hypothesized that aggressive meningiomas have unique DNA methylation patterns that could be used to better stratify patient management. Samples (n = 140) were profiled using the Illumina HumanMethylation450BeadChip. Unsupervised modeling on a training set (n = 89) identified 2 molecular methylation subgroups of meningioma (MM) with significantly different recurrence-free survival (RFS) times between the groups: a prognostically unfavorable subgroup (MM-UNFAV) and a prognostically favorable subgroup (MM-FAV)...
January 27, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28130638/marginal-vitamin-a-deficiency-facilitates-alzheimer-s-pathogenesis
#9
Jiaying Zeng, Li Chen, Zhe Wang, Qian Chen, Zhen Fan, Hongpeng Jiang, Yili Wu, Lan Ren, Jie Chen, Tingyu Li, Weihong Song
Deposition of amyloid β protein (Aβ) to form neuritic plaques in the brain is the unique pathological hallmark of Alzheimer's disease (AD). Aβ is derived from amyloid β precursor protein (APP) by β- and γ-secretase cleavages and turned over by glia in the central nervous system (CNS). Vitamin A deficiency (VAD) has been shown to affect cognitive functions. Marginal vitamin A deficiency (MVAD) is a serious and widespread public health problem among pregnant women and children in developing countries. However, the role of MVAD in the pathogenesis of AD remains elusive...
January 27, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28124097/pan-mutant-idh1-inhibitor-bay-1436032-for-effective-treatment-of-idh1-mutant-astrocytoma-in-vivo
#10
Stefan Pusch, Sonja Krausert, Viktoria Fischer, Jörg Balss, Martina Ott, Daniel Schrimpf, David Capper, Felix Sahm, Jessica Eisel, Ann-Christin Beck, Manfred Jugold, Viktoria Eichwald, Stefan Kaulfuss, Olaf Panknin, Hartmut Rehwinkel, Katja Zimmermann, Roman C Hillig, Judith Guenther, Luisella Toschi, Roland Neuhaus, Andrea Haegebart, Holger Hess-Stumpp, Markus Bauser, Wolfgang Wick, Andreas Unterberg, Christel Herold-Mende, Michael Platten, Andreas von Deimling
Mutations in codon 132 of isocitrate dehydrogenase (IDH) 1 are frequent in diffuse glioma, acute myeloid leukemia, chondrosarcoma and intrahepatic cholangiocarcinoma. These mutations result in a neomorphic enzyme specificity which leads to a dramatic increase of intracellular D-2-hydroxyglutarate (2-HG) in tumor cells. Therefore, mutant IDH1 protein is a highly attractive target for inhibitory drugs. Here, we describe the development and properties of BAY 1436032, a pan-inhibitor of IDH1 protein with different codon 132 mutations...
January 25, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28108787/dimethyl-fumarate-accelerates-peripheral-nerve-regeneration-via-activation-of-the-anti-inflammatory-and-cytoprotective-nrf2-ho-1-signaling-pathway
#11
LETTER
Fabian Szepanowski, Daniel M Donaldson, Hans-Peter Hartung, Anne K Mausberg, Christoph Kleinschnitz, Bernd C Kieseier, Mark Stettner
No abstract text is available yet for this article.
January 20, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28097436/damaged-reward-areas-in-human-alcoholics-neuronal-proportion-decline-and-astrocyte-activation
#12
LETTER
Daniil Sarkisyan, Igor Bazov, Hiroyuki Watanabe, Olga Kononenko, Ann-Christine Syvänen, Gunter Schumann, Tatiana Yakovleva, Georgy Bakalkin
No abstract text is available yet for this article.
January 17, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28091722/hyperphosphorylated-tau-causes-reduced-hippocampal-ca1-excitability-by-relocating-the-axon-initial-segment
#13
Robert John Hatch, Yan Wei, Di Xia, Jürgen Götz
Hyperphosphorylated tau has a critical role in tauopathies such as Alzheimer's disease and frontotemporal dementia, impairing neuronal function and eventually leading to neurodegeneration. A critical role for tau is supported by studies in transgenic mouse models that express the P301L tau mutation found in cases of familial frontotemporal dementia, with the accumulation of hyperphosphorylated tau in the hippocampus causing reductions in hippocampal long-term potentiation and impairments in spatial learning and memory...
January 16, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28083634/tau-interactome-mapping%C3%A2-based-identification-of-otub1-as-tau-deubiquitinase-involved-in-accumulation-of-pathological-tau-forms-in-vitro-and-in-vivo
#14
Peng Wang, Gerard Joberty, Arjan Buist, Alexandre Vanoosthuyse, Ilie-Cosmin Stancu, Bruno Vasconcelos, Nathalie Pierrot, Maria Faelth-Savitski, Pascal Kienlen-Campard, Jean-Noël Octave, Marcus Bantscheff, Gerard Drewes, Diederik Moechars, Ilse Dewachter
Dysregulated proteostasis is a key feature of a variety of neurodegenerative disorders. In Alzheimer's disease (AD), progression of symptoms closely correlates with spatiotemporal progression of Tau aggregation, with "early" oligomeric Tau forms rather than mature neurofibrillary tangles (NFTs) considered to be pathogenetic culprits. The ubiquitin-proteasome system (UPS) controls degradation of soluble normal and abnormally folded cytosolic proteins. The UPS is affected in AD and is identified by genomewide association study (GWAS) as a risk pathway for AD...
January 12, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28078450/genome-wide-methylation-profiles-in-primary-intracranial-germ-cell-tumors-indicate-a-primordial-germ-cell-origin-for-germinomas
#15
Shintaro Fukushima, Satoshi Yamashita, Hisato Kobayashi, Hirokazu Takami, Kohei Fukuoka, Taishi Nakamura, Kai Yamasaki, Yuko Matsushita, Hiromi Nakamura, Yasushi Totoki, Mamoru Kato, Tomonari Suzuki, Kazuhiko Mishima, Takaaki Yanagisawa, Akitake Mukasa, Nobuhito Saito, Masayuki Kanamori, Toshihiro Kumabe, Teiji Tominaga, Motoo Nagane, Toshihiko Iuchi, Koji Yoshimoto, Masahiro Mizoguchi, Kaoru Tamura, Keiichi Sakai, Kazuhiko Sugiyama, Mitsutoshi Nakada, Kiyotaka Yokogami, Hideo Takeshima, Yonehiro Kanemura, Masahide Matsuda, Akira Matsumura, Kazuhiko Kurozumi, Keisuke Ueki, Masahiro Nonaka, Akio Asai, Nobutaka Kawahara, Yuichi Hirose, Tatusya Takayama, Yoichi Nakazato, Yoshitaka Narita, Tatsuhiro Shibata, Masao Matsutani, Toshikazu Ushijima, Ryo Nishikawa, Koichi Ichimura
Intracranial germ cell tumors (iGCTs) are the second most common brain tumors among children under 14 in Japan. The World Health Organization classification recognizes several subtypes of iGCTs, which are conventionally subclassified into pure germinoma or non-germinomatous GCTs. Recent exhaustive genomic studies showed that mutations of the genes involved in the MAPK and/or PI3K pathways are common in iGCTs; however, the mechanisms of how different subtypes develop, often as a mixed-GCT, are unknown. To elucidate the pathogenesis of iGCTs, we investigated 61 GCTs of various subtypes by genome-wide DNA methylation profiling...
January 11, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28074273/experimental-models-of-neurological-disease-neuropathology-determines-what-is-virtual-reality-science-or-fiction
#16
EDITORIAL
Werner Paulus
No abstract text is available yet for this article.
January 10, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28070672/opposing-effects-of-progranulin-deficiency-on-amyloid-and-tau-pathologies-via-microglial-tyrobp-network
#17
Hideyuki Takahashi, Zoe A Klein, Sarah M Bhagat, Adam C Kaufman, Mikhail A Kostylev, Tsuneya Ikezu, Stephen M Strittmatter
Progranulin (PGRN) is implicated in Alzheimer's disease (AD) as well as frontotemporal lobar degeneration. Genetic studies demonstrate an association of the common GRN rs5848 variant that results in reduced PGRN levels with increased risk for AD. However, the mechanisms by which PGRN reduction from the GRN AD risk variant or mutation exacerbates AD pathophysiology remain ill defined. Here, we show that the GRN AD risk variant has no significant effects on florbetapir positron emission tomographic amyloid imaging and cerebrospinal fluid (CSF) Aβ levels, whereas it is associated with increased CSF tau levels in human subjects of the Alzheimer's disease neuroimaging initiative studies...
January 9, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28064358/incipient-progressive-supranuclear-palsy-is-more-common-than-expected-and-may-comprise-clinicopathological-subtypes-a-forensic-autopsy-series
#18
Koji Yoshida, Yukiko Hata, Koshi Kinoshita, Shutaro Takashima, Kortaro Tanaka, Naoki Nishida
We investigated 998 serial Japanese forensic autopsy cases (0-101 years old, mean age 61.7 ± 21.9), with no case selection, using immunohistochemistry to detect cases with progressive supranuclear palsy (PSP). Twenty-nine cases (mean age 82.3 ± 7.2 years, 11 males, 18 females) fulfilled the National Institute of Neuronal Disorders and Stroke (NINDS)-PSP pathological criteria (2.9% of all cases, 4.6% of cases over 60). All had neuronal and glial inclusions in the basal ganglia and brainstem. However, 13 cases had low tau pathology and were categorized as atypical PSP...
January 7, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28058507/als-ftld-experimental-models-and-reality
#19
REVIEW
Rachel H Tan, Yazi D Ke, Lars M Ittner, Glenda M Halliday
Amyotrophic lateral sclerosis is characterised by a loss of upper and lower motor neurons and characteristic muscle weakness and wasting, the most common form being sporadic disease with neuronal inclusions containing the tar DNA-binding protein 43 (TDP-43). Frontotemporal lobar degeneration is characterised by atrophy of the frontal and/or temporal lobes, the most common clinical form being the behavioural variant, in which neuronal inclusions containing either TDP-43 or 3-repeat tau are most prevalent. Although the genetic mutations associated with these diseases have allowed various experimental models to be developed, the initial genetic forms identified remain the most common models employed to date...
January 5, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28058506/genome-wide-dna-methylation-profiling-identifies-primary-central-nervous-system-lymphoma-as-a-distinct-entity-different-from-systemic-diffuse-large-b-cell-lymphoma
#20
LETTER
Taishi Nakamura, Satoshi Yamashita, Kazutaka Fukumura, Jun Nakabayashi, Kazuhiro Tanaka, Kaoru Tamura, Kensuke Tateishi, Manabu Kinoshita, Shintaro Fukushima, Hirokazu Takami, Kohei Fukuoka, Kai Yamazaki, Yuko Matsushita, Makoto Ohno, Yasuji Miyakita, Soichiro Shibui, Atsuhiko Kubo, Takashi Shuto, Sylvia Kocialkowski, Shoji Yamanaka, Akitake Mukasa, Takashi Sasayama, Kazuhiko Mishima, Taketoshi Maehara, Nobutaka Kawahara, Motoo Nagane, Yoshitaka Narita, Hiroyuki Mano, Toshikazu Ushijima, Koichi Ichimura
No abstract text is available yet for this article.
January 5, 2017: Acta Neuropathologica
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