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Journal of Neuropathology and Experimental Neurology

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https://www.readbyqxmd.com/read/28082327/a-functional-and-neuropathological-testing-paradigm-reveals-new-disability-based-parameters-and-histological-features-for-p0180-190-induced-experimental-autoimmune-neuritis-in-c57bl-6-mice
#1
David G Gonsalvez, Mithraka De Silva, Rhiannon J Wood, Lauren Giuffrida, Trevor J Kilpatrick, Simon S Murray, Junhua Xiao
We assessed novel disability-based parameters and neuropathological features of the P0180-190 peptide-induced model of experimental autoimmune neuritis (EAN) in C57BL/6 mice. We show that functional assessments such as running capacity provide a more sensitive method for detecting alterations in disease severity than a classical clinical scoring paradigm. We performed detailed ultrastructural analysis and show for the first time that tomaculous neuropathy is a neuropathological feature of this disease model...
January 12, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28082326/friedreich-ataxia-hypoplasia-of-spinal-cord-and-dorsal-root-ganglia
#2
Arnulf H Koeppen, Alyssa B Becker, Jiang Qian, Paul J Feustel
After Friedreich's description in 1877, depletion of myelinated fibers in the dorsal columns, dorsal spinocerebellar and lateral corticospinal tracts, and neuronal loss in the dorsal nuclei of Clarke columns were considered unique and essential neuropathological features of Friedreich ataxia (FA). Lack of large neurons in dorsal root ganglia (DRG), thinning of dorsal roots (DR), and poor myelination in sensory nerves are now recognized as key components of FA. Here, we measured cross-sectional areas of the mid-thoracic spinal cord (SC) and neuronal sizes in lumbosacral DRG of 24 genetically confirmed FA cases...
January 12, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28069931/the-search-for-a-peripheral-biopsy-indicator-of-%C3%AE-synuclein-pathology-for-parkinson-disease
#3
REVIEW
John M Lee, Pascal Derkinderen, Jeffrey H Kordower, Roy Freeman, David G Munoz, Thomas Kremer, Wagner Zago, Samantha J Hutten, Charles H Adler, Geidy E Serrano, Thomas G Beach
The neuropathological hallmark of Parkinson disease (PD) is abnormal accumulation of α-synuclein (α-syn). Demonstrating pathological α-syn in live patients would be useful for identifying and monitoring PD patients. To date, however, imaging and biofluid approaches have not permitted premortem assessment of pathological α-syn. α-syn pathology in the peripheral nervous system of patients with PD has been demonstrated in studies dating back more than 40 years. More recent work suggests that colon, submandibular gland and skin biopsies could be useful as expedient biomarkers but histological differentiation of pathological and normal peripheral α-syn has been challenging and multiple research groups have reported variable results...
January 9, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28069930/a-quantitative-analysis-of-brain-soluble-tau-and-the-tau-secretion-factor
#4
Pengcheng Han, Geidy Serrano, Thomas G Beach, Richard J Caselli, Junxiang Yin, Ningning Zhuang, Jiong Shi
Neurofibrillary tangles (NFTs) represent products of insoluble tau protein in the brains of patients with Alzheimer disease (AD). The cerebrospinal fluid (CSF) tau level is a biomarker in AD diagnosis. The soluble portion of tau protein in brain parenchyma is presumably the source for CSF tau but this has not previously been quantified. We measured CSF tau and soluble brain tau at autopsy in temporal and frontal brain tissue samples from 7 cognitive normal, 12 mild cognitively impaired, and 19 AD subjects. Based on the measured brain soluble tau, we calculated the whole brain tau load and estimated tau secretion factor...
January 9, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28069929/genomic-alterations-of-adamantinomatous-and-papillary-craniopharyngioma
#5
Tobias Goschzik, Marco Gessi, Verena Dreschmann, Ursel Gebhardt, Linghua Wang, Shigeru Yamaguchi, David A Wheeler, Libero Lauriola, Ching C Lau, Hermann L Müller, Torsten Pietsch
Craniopharyngiomas are rare histologically benign but clinically challenging neoplasms. To obtain further information on the molecular genetics and biology of craniopharyngiomas, we analyzed a cohort of 121 adamantinomatous and 16 papillary craniopharyngiomas (ACP, PCP). We extracted DNA from formalin-fixed paraffin-embedded tissue and determined mutational status of CTNNB1, BRAF, and DDX3X by Sanger sequencing, next generation panel sequencing, and pyrosequencing. Sixteen craniopharyngiomas were further analyzed by molecular inversion profiling (MIP); 76...
January 9, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28062571/performance-of-a-condensed-protocol-that-reduces-effort-and-cost-of-nia-aa-guidelines-for-neuropathologic-assessment-of-alzheimer-disease
#6
Margaret E Flanagan, Desiree A Marshall, Jane B Shofer, Kathleen S Montine, Peter T Nelson, Thomas J Montine, C Dirk Keene
Concerns regarding resource expenditures have been expressed about the 2012 NIA-AA Sponsored Guidelines for neuropathologic assessment of Alzheimer disease (AD) and related dementias. Here, we investigated a cost-reducing Condensed Protocol and its effectiveness in maintaining the diagnostic performance of Guidelines in assessing AD, Lewy body disease (LBD), microvascular brain injury, hippocampal sclerosis (HS), and congophilic amyloid angiopathy (CAA). The Condensed Protocol consolidates the same 20 regions into 5 tissue cassettes at ∼75% lower cost...
January 6, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28053004/dna-methylation-profiles-of-selected-pro-inflammatory-cytokines-in-alzheimer-disease
#7
Vincenzina Nicolia, Rosaria A Cavallaro, Irene López-González, Mauro Maccarrone, Sigfrido Scarpa, Isidre Ferrer, Andrea Fuso
By means of functional genomics analysis, we recently described the mRNA expression profiles of various genes involved in the neuroinflammatory response in the brains of subjects with late-onset Alzheimer Disease (LOAD). Some of these genes, namely interleukin (IL)-1β and IL-6, showed distinct expression profiles with peak expression during the first stages of the disease and control-like levels at later stages. IL-1β and IL-6 genes are modulated by DNA methylation in different chronic and degenerative diseases; it is also well known that LOAD may have an epigenetic basis...
January 4, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28040794/native-oligodendrocytes-in-astrocytomas-might-inhibit-tumor-proliferation-by-wif1-expression
#8
Martin Asslaber, Silvia Schauer, Margit Gogg-Kamerer, Eva Bernhart, Franz Quehenberger, Johannes Haybaeck
Malignant astrocytoma remains incurable and rapidly fatal despite multimodal therapy. In particular, accelerated tumor cell heterogeneity often overcomes therapeutic effects of molecular protein targeting. This study aimed at identifying a gene with therapeutic potential that was consistently downregulated with astrocytoma progression. Analysis of the "Rembrandt" gene expression data revealed Wnt inhibitory factor 1 (WIF1) gene as the most promising candidate with tumor suppressor function. Consequently, 288 randomly selected tissue regions of astrocytoma specimens were investigated immunohistochemically with the aid of image analysis...
December 31, 2016: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28040793/tert-promoter-mutations-but-not-the-alternative-lengthening-of-telomeres-phenotype-are-present-in-a-subset-of-ependymomas-and-are-associated-with-adult-onset-and-progression-to-ependymosarcoma
#9
Fabienne Brügger, Matthias S Dettmer, Maja Neuenschwander, Aurel Perren, Ilaria Marinoni, Ekkehard Hewer
Genetic signatures related to telomere maintenance have emerged as powerful classifiers among CNS tumors. These include the alternative lengthening of telomeres (ALT) phenotype associated with mutations in the ATRX and DAXX genes and recurrent point mutations in the TERT gene promoter. We investigated a patient cohort covering the entire spectrum of childhood and adult ependymomas (n = 128), including subependymomas and myxopapillary ependymomas, for the presence of TERT promoter mutations, for loss of ATRX or DAXX expression by immunohistochemistry (as surrogates as underlying gene mutations), and for the ALT phenotype by fluorescence in situ hybridization (FISH)...
December 31, 2016: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28040792/autophagy-in-tri-o-cresyl-phosphate-induced-delayed-neurotoxicity
#10
Hai-Yang Xu, Pan Wang, Ying-Jian Sun, Lu Jiang, Ming-Yuan Xu, Yi-Jun Wu
The widely used organophosphorus compound tri-o-cresyl phosphate (TOCP) elicits delayed neurotoxicity characterized by progressive axonal degeneration in the spinal cord and peripheral nerves. However, the precise mechanisms of TOCP-induced delayed neurotoxicity are not clear. Because autophagy has been linked to the pathogenesis of neurodegenerative diseases, we aimed to characterize autophagy in the progression of TOCP-induced delayed neurotoxicity. In vivo experiments using the adult hen animal model showed that autophagy in spinal cord axons and in sciatic nerves was markedly induced at the early preclinical stage of TOCP-induced delayed neurotoxicity; it was decreased as the delayed neurotoxicity progressed to the overt neuropathy stage...
December 31, 2016: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28025236/otx2-defines-a-subgroup-of-atypical-teratoid-rhabdoid-tumors-with-close-relationship-to-choroid-plexus-tumors
#11
Anna Sophia Japp, Ludger Klein-Hitpass, Dorota Denkhaus, Torsten Pietsch
Atypical teratoid rhabdoid tumors (ATRT) are highly malignant brain tumors of early childhood that have been regarded as a homogenous entity characterized by inactivation of the SMARCB1/INI1 or SMARCA4/BRG1 genes as the only characteristic alteration. Recent studies suggest that similar to other embryonal tumors ATRT can also be divided into subgroups based on their mRNA or methylation profiles. Using microarray-based expression analysis of 12 patient ATRT specimens we demonstrated the existence of 2 subgroups of ATRT...
December 26, 2016: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/27818385/contactin-associated-protein-1-cntnap1-mutations-induce-characteristic-lesions-of-the-paranodal-region
#12
Jean-Michel Vallat, Mathilde Nizon, Alex Magee, Bertrand Isidor, Laurent Magy, Yann Péréon, Laurence Richard, Robert Ouvrier, Benjamin Cogné, Jérôme Devaux, Stephan Zuchner, Stéphane Mathis
Congenital hypomyelinating neuropathy is a rare neonatal syndrome responsible for hypotonia and weakness. Nerve microscopic examination shows amyelination or hypomyelination. Recently, mutations in CNTNAP1 have been described in a few patients. CNTNAP1 encodes contactin-associated protein 1 (caspr-1), which is an essential component of the paranodal junctions of the peripheral and central nervous systems, and is necessary for the establishment of transverse bands that stabilize paranodal axo-glial junctions...
November 6, 2016: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/27815397/new-strategy-that-delays-progression-of-amyotrophic-lateral-sclerosis-in-g1h-g93a-transgenic-mice-oral-administration-of-xanthine-oxidoreductase-inhibitors-that-are-not-substrates-for-the-purine-salvage-pathway
#13
Shinsuke Kato, Masako Kato, Teruo Kusano, Takeshi Nishino
Amyotrophic lateral sclerosis (ALS), Lou Gehrig's disease, is a progressive fatal neurodegenerative disease that involves both upper and lower motor neurons. We orally administered 4 xanthine oxidoreductase (XOR) inhibitors to G1H-G93A mice carrying 25 transgene copy numbers of human mutant G93A superoxide dismutase 1, from 80 days of age. Three nonpurine-analogue inhibitors (TEI-6720: Febuxostat, Y-700 and FYX-051), but not allopurinol with a purine analogue ring (pyrazolo pyrimidine ring), significantly delayed disease onset, prolonged survival and the duration of disease stages, improved clinical signs, and alleviated weight loss...
November 4, 2016: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/27815396/quantitative-analysis-of-the-cellular-microenvironment-of-glioblastoma-to-develop-predictive-statistical-models-of-overall-survival
#14
Jessica X Yuan, Fahad F Bafakih, James W Mandell, Bethany J Horton, Jennifer M Munson
Glioblastomas, the most common primary malignant brain tumors, have a distinct tissue microenvironment. Although non-neoplastic cells contribute to glioblastoma progression, very few quantitative studies have shown the effect of tumor microenvironmental influences on patient survival. We examined relationships of the cellular microenvironment, including astrocytes, microglia, oligodendrocytes, and blood vessels, to survival in glioblastoma patients. Using histological staining and quantitative image analyses, we examined the tumor-associated parenchyma of 33 patients and developed statistical models to predict patient outcomes based on the cellular picture of the tumor parenchyma...
November 4, 2016: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/27815395/chronic-traumatic-encephalopathy-like-abnormalities-in-a-routine-neuropathology-service
#15
Shawna Noy, Sherry Krawitz, Marc R Del Bigio
Chronic traumatic encephalopathy (CTE) has been described mainly in professional athletes and military personnel and is characterized by deposition of hyperphosphorylated tau at the depths of cortical sulci and around blood vessels. To assess CTE-like changes in a routine neuropathology service, we prospectively examined 111 brains (age 18-60 years). The presence of tau-immunoreactive deposits was staged using guidelines described by others and was correlated with the medical history. 72/111 cases were negative for CTE-like changes; 34/111 were CTE stage <1; 3/111 were CTE stage 1; and 2/111 were CTE stage 2...
November 4, 2016: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/27807004/endothelial-cell-hypertrophy-and-microvascular-proliferation-in-meningiomas-are-correlated-with-higher-histological-grade-and-shorter-progression-free-survival
#16
Catherine Ling, Celso Pouget, Fabien Rech, Robin Pflaum, Mathilde Treffel, Franck Bielle, Karima Mokhtari, Jean-Matthieu Casse, Jean-Michel Vignaud, Michel Kalamarides, Matthieu Peyre, Guillaume Gauchotte
Microvascular proliferation (MVP) is a hallmark of glioblastoma. Endothelial cell hypertrophy (ECH), also known as endothelial hyperplasia, is correlated with a shorter survival of patients with gliomas. However, the prognostic value of these 2 morphological features has not been studied in meningiomas. The aim of this study was to evaluate the prognostic value of angiogenesis in meningiomas, most notably ECH, MVP, and microvascular density, which were evaluated using immunohistochemistry with antibodies against CD34 and CD105 (a marker of neovascularization) in a series of 139 meningiomas...
November 2, 2016: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/27941141/tenascin-c-is-associated-with-cored-amyloid-%C3%AE-plaques-in-alzheimer-disease-and-pathology-burdened-cognitively-normal-elderly
#17
(no author information available yet)
No abstract text is available yet for this article.
December 2016: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/27941140/appreciation-of-reviewers
#18
LETTER
(no author information available yet)
No abstract text is available yet for this article.
December 2016: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/27941139/prognostic-biomarkers-in-spinal-chordoma-a-systematic-review
#19
LETTER
Ming-Xiang Zou, Guo-Hua Lv, Xiao-Bin Wang, Jing Li
No abstract text is available yet for this article.
December 2016: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/27941138/examining-neuropathology-beginning-a-dialogue
#20
REVIEW
Clayton Wiley, Michael N Hart, Karen M Weidenheim, David N Louis, Sunhee C Lee
No abstract text is available yet for this article.
December 2016: Journal of Neuropathology and Experimental Neurology
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