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Acta Neuropathologica

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https://www.readbyqxmd.com/read/29450647/rna-versus-protein-toxicity-in-c9orf72-als-ftld
#1
LETTER
Thomas Arzberger, Martin H Schludi, Carina Lehmer, Bettina Schmid, Dieter Edbauer
No abstract text is available yet for this article.
February 15, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29450646/evidence-of-amyloid-%C3%AE-cerebral-amyloid-angiopathy-transmission-through-neurosurgery
#2
Zane Jaunmuktane, Annelies Quaegebeur, Ricardo Taipa, Miguel Viana-Baptista, Raquel Barbosa, Carolin Koriath, Raf Sciot, Simon Mead, Sebastian Brandner
Amyloid-β (Aβ) is a peptide deposited in the brain parenchyma in Alzheimer's disease and in cerebral blood vessels, causing cerebral amyloid angiopathy (CAA). Aβ pathology is transmissible experimentally in animals and through medical procedures in humans, such as contaminated growth hormone or dura mater transplantation in the context of iatrogenic prion disease. Here, we present four patients who underwent neurosurgical procedures during childhood or teenage years and presented with intracerebral haemorrhage approximately three decades later, caused by severe CAA...
February 15, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29441412/progressive-multiple-sclerosis-patients-show-substantial-lesion-activity-that-correlates-with-clinical-disease-severity-and-sex-a-retrospective-autopsy-cohort-analysis
#3
Sabina Luchetti, Nina L Fransen, Corbert G van Eden, Valeria Ramaglia, Matthew Mason, Inge Huitinga
Multiple sclerosis (MS) is a highly heterogeneous disease with large inter-individual differences in disease course. MS lesion pathology shows considerable heterogeneity in localization, cellular content and degree of demyelination between patients. In this study, we investigated pathological correlates of disease course in MS using the autopsy cohort of the Netherlands Brain Bank (NBB), containing 182 MS brain donors. Using a standardized autopsy procedure including systematic dissection from standard locations, 3188 tissue blocks containing 7562 MS lesions were dissected...
February 13, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29435664/deep-sequencing-of-wnt-activated-medulloblastomas-reveals-secondary-shh-pathway-activation
#4
LETTER
J Bryan Iorgulescu, Jessica Van Ziffle, Meredith Stevers, James P Grenert, Boris C Bastian, Lukas Chavez, Damian Stichel, Ivo Buchhalter, David Samuel, Theodore Nicolaides, Anuradha Banerjee, Sabine Mueller, Nalin Gupta, Tarik Tihan, Andrew W Bollen, Paul A Northcott, Marcel Kool, Stefan Pfister, Andrey Korshunov, Arie Perry, David A Solomon
No abstract text is available yet for this article.
February 12, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29428975/5-hydroxymethylcytosine-preferentially-targets-genes-upregulated-in-isocitrate-dehydrogenase-1-mutant-high-grade-glioma
#5
Wioletta K Glowacka, Harshika Jain, Makiko Okura, Abulizi Maimaitiming, Yasin Mamatjan, Romina Nejad, Hamza Farooq, Michael D Taylor, Kenneth Aldape, Paul Kongkham
Gliomas demonstrate epigenetic dysregulation exemplified by the Glioma CpG Island Methylator Phenotype (G-CIMP) seen in IDH1 mutant tumors. 5-Hydroxymethylcytosine (5hmC) is implicated in glioma pathogenesis; however, its role in IDH1 mutant gliomas is incompletely understood. To characterize 5hmC in IDH1 mutant gliomas further, we examine 5hmC in a cohort of IDH1 mutant and wild-type high-grade gliomas (HGG) using a quantitative locus-specific approach. Regions demonstrating high 5hmC abundance and differentially hydroxymethylated regions (DHMR) enrich for enhancers implicated in glioma pathogenesis...
February 10, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29428974/malignant-rhabdoid-tumors-originating-within-and-outside-the-central-nervous-system-are-clinically-and-molecularly-heterogeneous
#6
Emilia M Pinto, Dima Hamideh, Armita Bahrami, Brent A Orr, Tong Lin, Stanley Pounds, Gerard P Zambetti, Alberto S Pappo, Amar Gajjar, Sameer Agnihotri, Alberto Broniscer
Multifocal synchronous or metachronous atypical teratoid rhabdoid tumors (ATRTs) and non-central nervous system malignant rhabdoid tumors (extra-CNS MRTs) are rare cancers. We reviewed the clinical and radiologic characteristics of affected patients seen at our institution. Genotyping and analysis of copy number abnormalities (CNAs) in SMARCB1 were performed in germline and tumor samples. Tumor samples underwent genome-wide DNA methylation and CNA analysis. The median age at diagnosis of 21 patients was 0.6 years...
February 10, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29428973/multinodular-and-vacuolating-neuronal-tumor-of-the-cerebrum-is-a-clonal-neoplasm-defined-by-genetic-alterations-that-activate-the-map-kinase-signaling-pathway
#7
LETTER
Melike Pekmezci, Meredith Stevers, Joanna J Phillips, Jessica Van Ziffle, Boris C Bastian, Nadejda M Tsankova, Bette K Kleinschmidt-DeMasters, Marc K Rosenblum, Tarik Tihan, Arie Perry, David A Solomon
No abstract text is available yet for this article.
February 10, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29428972/the-role-of-brain-barriers-in-fluid-movement-in-the-cns-is-there-a-glymphatic-system
#8
REVIEW
N Joan Abbott, Michelle E Pizzo, Jane E Preston, Damir Janigro, Robert G Thorne
Brain fluids are rigidly regulated to provide stable environments for neuronal function, e.g., low K+, Ca2+, and protein to optimise signalling and minimise neurotoxicity. At the same time, neuronal and astroglial waste must be promptly removed. The interstitial fluid (ISF) of the brain tissue and the cerebrospinal fluid (CSF) bathing the CNS are integral to this homeostasis and the idea of a glia-lymph or 'glymphatic' system for waste clearance from brain has developed over the last 5 years. This links bulk (convective) flow of CSF into brain along the outside of penetrating arteries, glia-mediated convective transport of fluid and solutes through the brain extracellular space (ECS) involving the aquaporin-4 (AQP4) water channel, and finally delivery of fluid to venules for clearance along peri-venous spaces...
February 10, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29423877/nhlrc2-variants-identified-in-patients-with-fibrosis-neurodegeneration-and-cerebral-angiomatosis-finca-characterisation-of-a-novel-cerebropulmonary-disease
#9
Johanna Uusimaa, Riitta Kaarteenaho, Teija Paakkola, Hannu Tuominen, Minna K Karjalainen, Javad Nadaf, Teppo Varilo, Meri Uusi-Mäkelä, Maria Suo-Palosaari, Ilkka Pietilä, Anniina E Hiltunen, Lloyd Ruddock, Heli Alanen, Ekaterina Biterova, Ilkka Miinalainen, Annamari Salminen, Raija Soininen, Aki Manninen, Raija Sormunen, Mika Kaakinen, Reetta Vuolteenaho, Riitta Herva, Päivi Vieira, Teija Dunder, Hannaleena Kokkonen, Jukka S Moilanen, Heikki Rantala, Lawrence M Nogee, Jacek Majewski, Mika Rämet, Mikko Hallman, Reetta Hinttala
A novel multi-organ disease that is fatal in early childhood was identified in three patients from two non-consanguineous families. These children were born asymptomatic but at the age of 2 months they manifested progressive multi-organ symptoms resembling no previously known disease. The main clinical features included progressive cerebropulmonary symptoms, malabsorption, progressive growth failure, recurrent infections, chronic haemolytic anaemia and transient liver dysfunction. In the affected children, neuropathology revealed increased angiomatosis-like leptomeningeal, cortical and superficial white matter vascularisation and congestion, vacuolar degeneration and myelin loss in white matter, as well as neuronal degeneration...
February 8, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29411111/functional-morphology-of-the-blood-brain-barrier-in-health-and-disease
#10
REVIEW
Stefan Liebner, Rick M Dijkhuizen, Yvonne Reiss, Karl H Plate, Dritan Agalliu, Gabriela Constantin
The adult quiescent blood-brain barrier (BBB), a structure organised by endothelial cells through interactions with pericytes, astrocytes, neurons and microglia in the neurovascular unit, is highly regulated but fragile at the same time. In the past decade, there has been considerable progress in understanding not only the molecular pathways involved in BBB development, but also BBB breakdown in neurological diseases. Specifically, the Wnt/β-catenin, retinoic acid and sonic hedgehog pathways moved into the focus of BBB research...
February 6, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29397421/activin-receptors-regulate-the-oligodendrocyte-lineage-in-health-and-disease
#11
Alessandra Dillenburg, Graeme Ireland, Rebecca K Holloway, Claire L Davies, Frances L Evans, Matthew Swire, Marie E Bechler, Daniel Soong, Tracy J Yuen, Gloria H Su, Julie-Clare Becher, Colin Smith, Anna Williams, Veronique E Miron
The most prevalent neurological disorders of myelin include perinatal brain injury leading to cerebral palsy in infants and multiple sclerosis in adults. Although these disorders have distinct etiologies, they share a common neuropathological feature of failed progenitor differentiation into myelin-producing oligodendrocytes and lack of myelin, for which there is an unmet clinical need. Here, we reveal that a molecular pathology common to both disorders is dysregulation of activin receptors and that activin receptor signaling is required for the majority of myelin generation in development and following injury...
February 3, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29397420/cluster-barriers-of-the-central-nervous-system
#12
EDITORIAL
Britta Engelhardt
No abstract text is available yet for this article.
February 3, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29392445/correction-to-paragangliomas-arise-through-an-autonomous-vasculo-angio-neurogenic-program-inhibited-by-imatinib
#13
Fabio Verginelli, Silvia Perconti, Simone Vespa, Francesca Schiavi, Sampath Chandra Prasad, Paola Lanuti, Alessandro Cama, Lorenzo Tramontana, Diana Liberata Esposito, Simone Guarnieri, Artenca Sheu, Mattia Russel Pantalone, Rosalba Florio, Annalisa Morgano, Cosmo Rossi, Giuseppina Bologna, Marco Marchisio, Andrea D'Argenio, Elisa Taschin, Rosa Visone, Giuseppe Opocher, Angelo Veronese, Carlo T Paties, Vinagolu K Rajasekhar, Cecilia Söderberg-Nauclér, Mario Sanna, Lavinia Vittoria Lotti, Renato Mariani-Costantini
The given and family names of two co-authors were incorrect in the published article. The correct spelling should read as: Sampath Chandra Prasad and Vinagolu K Rajasekhar.
February 1, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29380049/sense-and-antisense-rna-are-not-toxic-in-drosophila-models-of-c9orf72-associated-als-ftd
#14
Thomas G Moens, Sarah Mizielinska, Teresa Niccoli, Jamie S Mitchell, Annora Thoeng, Charlotte E Ridler, Sebastian Grönke, Jacqueline Esser, Amanda Heslegrave, Henrik Zetterberg, Linda Partridge, Adrian M Isaacs
A GGGGCC hexanucleotide repeat expansion in the C9orf72 gene is the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. Neurodegeneration may occur via transcription of the repeats into inherently toxic repetitive sense and antisense RNA species, or via repeat-associated non-ATG initiated translation (RANT) of sense and antisense RNA into toxic dipeptide repeat proteins. We have previously demonstrated that regular interspersion of repeat RNA with stop codons prevents RANT (RNA-only models), allowing us to study the role of repeat RNA in isolation...
January 29, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29372318/cimpact-now-update-1-not-otherwise-specified-nos-and-not-elsewhere-classified-nec
#15
LETTER
David N Louis, Pieter Wesseling, Werner Paulus, Caterina Giannini, Tracy T Batchelor, J Gregory Cairncross, David Capper, Dominique Figarella-Branger, M Beatriz Lopes, Wolfgang Wick, Martin van den Bent
No abstract text is available yet for this article.
January 25, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29368214/the-meninges-as-barriers-and-facilitators-for-the-movement-of-fluid-cells-and-pathogens-related-to-the-rodent-and-human-cns
#16
REVIEW
Roy O Weller, Matthew M Sharp, Myron Christodoulides, Roxana O Carare, Kjeld Møllgård
Meninges that surround the CNS consist of an outer fibrous sheet of dura mater (pachymeninx) that is also the inner periosteum of the skull. Underlying the dura are the arachnoid and pia mater (leptomeninges) that form the boundaries of the subarachnoid space. In this review we (1) examine the development of leptomeninges and their role as barriers and facilitators in the foetal CNS. There are two separate CSF systems during early foetal life, inner CSF in the ventricles and outer CSF in the subarachnoid space...
January 24, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29368213/molecular-anatomy-and-functions-of-the-choroidal-blood-cerebrospinal-fluid-barrier-in-health-and-disease
#17
REVIEW
Jean-François Ghersi-Egea, Nathalie Strazielle, Martin Catala, Violeta Silva-Vargas, Fiona Doetsch, Britta Engelhardt
The barrier between the blood and the ventricular cerebrospinal fluid (CSF) is located at the choroid plexuses. At the interface between two circulating fluids, these richly vascularized veil-like structures display a peculiar morphology explained by their developmental origin, and fulfill several functions essential for CNS homeostasis. They form a neuroprotective barrier preventing the accumulation of noxious compounds into the CSF and brain, and secrete CSF, which participates in the maintenance of a stable CNS internal environment...
January 24, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29368212/the-dna-methylome-of-ddr-genes-and-benefit-from-rt-or-tmz-in-idh-mutant-low-grade-glioma-treated-in-eortc-22033
#18
Pierre Bady, Sebastian Kurscheid, Mauro Delorenzi, Thierry Gorlia, Martin J van den Bent, Khê Hoang-Xuan, Élodie Vauléon, Anja Gijtenbeek, Roelien Enting, Brian Thiessen, Olivier Chinot, Frédéric Dhermain, Alba A Brandes, Jaap C Reijneveld, Christine Marosi, Martin J B Taphoorn, Wolfgang Wick, Andreas von Deimling, Pim French, Roger Stupp, Brigitta G Baumert, Monika E Hegi
The optimal treatment for patients with low-grade glioma (LGG) WHO grade II remains controversial. Overall survival ranges from 2 to over 15 years depending on molecular and clinical factors. Hence, risk-adjusted treatments are required for optimizing outcome and quality of life. We aim at identifying mechanisms and associated molecular markers predictive for benefit from radiotherapy (RT) or temozolomide (TMZ) in LGG patients treated in the randomized phase III trial EORTC 22033. As candidate biomarkers for these genotoxic treatments, we considered the DNA methylome of 410 DNA damage response (DDR) genes...
January 24, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29350274/t-lymphocytes-facilitate-brain-metastasis-of-breast-cancer-by-inducing-guanylate-binding-protein-1-expression
#19
Dana A M Mustafa, Rute M S M Pedrosa, Marcel Smid, Marcel van der Weiden, Vanja de Weerd, Alex L Nigg, Cor Berrevoets, Lona Zeneyedpour, Neibla Priego, Manuel Valiente, Theo M Luider, Reno Debets, John W M Martens, John A Foekens, Anieta M Sieuwerts, Johan M Kros
The discovery of genes and molecular pathways involved in the formation of brain metastasis would direct the development of therapeutic strategies to prevent this deadly complication of cancer. By comparing gene expression profiles of Estrogen Receptor negative (ER-) primary breast tumors between patients who developed metastasis to brain and to organs other than brain, we found that T lymphocytes promote the formation of brain metastases. To functionally test the ability of T cells to promote brain metastasis, we used an in vitro blood-brain barrier (BBB) model...
January 19, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29327084/bace1-inhibition-more-effectively-suppresses-initiation-than-progression-of-%C3%AE-amyloid-pathology
#20
Finn Peters, Hazal Salihoglu, Eva Rodrigues, Etienne Herzog, Tanja Blume, Severin Filser, Mario Dorostkar, Derya R Shimshek, Nils Brose, Ulf Neumann, Jochen Herms
BACE1 is the rate-limiting protease in the production of synaptotoxic β-amyloid (Aβ) species and hence one of the prime drug targets for potential therapy of Alzheimer's disease (AD). However, so far pharmacological BACE1 inhibition failed to rescue the cognitive decline in mild-to-moderate AD patients, which indicates that treatment at the symptomatic stage might be too late. In the current study, chronic in vivo two-photon microscopy was performed in a transgenic AD model to monitor the impact of pharmacological BACE1 inhibition on early β-amyloid pathology...
January 11, 2018: Acta Neuropathologica
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