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Mediators of cerebral hypoperfusion and blood‐brain barrier leakiness in alzheimer’s disease, vascular dementia and mixed dementia Brain Pathol. (IF 5.568) Pub Date : 2021-01-07 Hannah Tayler; J. Scott Miners; Özge Güzel; Rob MacLachlan; Seth Love
In vascular dementia (VaD) and Alzheimer’s disease (AD), cerebral hypoperfusion and blood‐brain barrier (BBB) leakiness contribute to brain damage. In this study, we have measured biochemical markers and mediators of cerebral hypoperfusion and BBB in the frontal (BA6) and parietal (BA7) cortex and underlying white matter, to investigate the pathophysiology of vascular dysfunction in AD, VaD and mixed
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Primary age‐related tauopathy (PART) in the general autopsy setting: Not just a disease of the elderly Brain Pathol. (IF 5.568) Pub Date : 2020-11-04 William O. Humphrey; Rachel Martindale; William W. Pendlebury; John C. DeWitt
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Oligodendrocyte‐specific deletion of FGFR2 ameliorates MOG35‐55‐induced EAE through ERK and Akt signalling Brain Pathol. (IF 5.568) Pub Date : 2020-10-26 Salar Kamali; Ranjithkumar Rajendran; Christine Stadelmann; Srikanth Karnati; Vinothkumar Rajendran; Mario Giraldo‐Velasquez; Martin Berghoff
Fibroblast growth factors (FGFs) and their receptors (FGFRs) are involved in demyelinating pathologies including multiple sclerosis (MS). In our recent study, oligodendrocyte‐specific deletion of FGFR1 resulted in a milder disease course, less inflammation, reduced myelin and axon damage in EAE. The objective of this study was to elucidate the role of oligodendroglial FGFR2 in MOG35‐55‐induced EAE
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Expanding the spectrum of EWSR1‐PATZ1 rearranged CNS tumors: an infantile case with leptomeningeal dissemination Brain Pathol. (IF 5.568) Pub Date : 2020-12-30 Sabrina Rossi; Sabina Barresi; Isabella Giovannoni; Viola Alesi; Andrea Ciolfi; Giovanna Stefania Colafati; Francesca Diomedi‐Camassei; Evelina Miele; Antonella Cacchione; Denise Quacquarini; Andrea Carai; Marco Tartaglia; Caterina Giannini; Felice Giangaspero; Angela Mastronuzzi; Rita Alaggio
EWSR1‐PATZ1 fusions, first described in small round or spindle cell sarcomas (2) have recently been reported in rare low‐ and high‐grade CNS tumors (2,4‐5,7‐9). Among the cerebral cases, only three have been provided with a complete clinico‐pathological description (7,9). We report a case of EWSR1‐PATZ1 brain tumor displaying unique clinico‐pathological and molecular features.
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Contribution of the astrocytic tau pathology to synapse loss in progressive supranuclear palsy and corticobasal degeneration Brain Pathol. (IF 5.568) Pub Date : 2020-10-22 Nils Briel; Katrin Pratsch; Sigrun Roeber; Thomas Arzberger; Jochen Herms
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Postmortem neuropathology in COVID‐19 Brain Pathol. (IF 5.568) Pub Date : 2020-10-23 David S. Younger
Dear Editor, This study concerns the clinicopathologic correlation of 50 decedents of 2019 coronavirus disease (COVID‐19) due to severe acute respiratory syndrome‐coronavirus‐2 (SARS‐CoV‐2) from among 250 reported patients succumbing to COVID‐19 illness (1-7) who underwent detailed postmortem neuropathological studies. This disease, which starts in the lungs, is a multisystem disorder affecting all
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Alleviation of extensive visual pathway dysfunction by a remyelinating drug in a chronic mouse model of multiple sclerosis Brain Pathol. (IF 5.568) Pub Date : 2020-12-23 Maria T. Sekyi; Kelli Lauderdale; Kelley C. Atkinson; Batis Golestany; Hawra Karim; Micah Feri; Joselyn S. Soto; Cobi Diaz; Sung Hoon Kim; Marianne Cilluffo; Steven Nusinowitz; John A. Katzenellenbogen; Seema K. Tiwari‐Woodruff
Visual deficits are among the most prevalent symptoms in patients with multiple sclerosis (MS). To understand deficits in the visual pathway during MS and potential treatment effects, we used experimental autoimmune encephalomyelitis (EAE), the most commonly used animal model of MS. The afferent visual pathway was assessed in vivo using optical coherence tomography (OCT), electroretinography (ERG)
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Mitochondrial DNA variants in inclusion body myositis characterized by deep sequencing Brain Pathol. (IF 5.568) Pub Date : 2020-12-22 Carola Hedberg‐Oldfors; Ulrika Lindgren; Swaraj Basu; Kittichate Visuttijai; Christopher Lindberg; Maria Falkenberg; Erik Larsson Lekholm; Anders Oldfors
Muscle pathology in inclusion body myositis (IBM) typically includes inflammatory cell infiltration, muscle fibers with rimmed vacuoles and cytochrome c oxidase (COX)‐deficient fibers. Previous studies have revealed clonal expansion of large mitochondrial DNA (mtDNA) deletions in the COX‐deficient muscle fibers. Technical limitations have prevented complete investigations of the mtDNA deletions and
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Heterogeneity of cellular inflammatory responses in ageing white matter and relationship to alzheimer’s and small vessel disease pathologies Brain Pathol. (IF 5.568) Pub Date : 2020-12-17 R Waller; R Narramore; JE Simpson; PR Heath; N Verma; M Tinsley; J Barnes; H Haris; FE Henderson; FE Matthews; CD Richardson; C Brayne; PG Ince; R Kalaria; SB Wharton;
White matter lesions (WML) are common in the ageing brain, often arising in a field effect of diffuse white matter abnormality. Although WML are associated with cerebral small vessel disease (SVD) and Alzheimer’s disease (AD), their cause and pathogenesis remain unclear. The current study tested the hypothesis that different patterns of neuroinflammation are associated with SVD compared to AD neuropathology
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Prognostic relevance of adding MRI data to WHO 2016 and cIMPACT‐NOW updates for diffuse astrocytic tumours in adults. Working towards the extended use of MRI data in integrated glioma diagnosis. Brain Pathol. (IF 5.568) Pub Date : 2020-12-17 Alexandre Roux; Stéphane Tran; Myriam Edjlali; Raphaël Saffroy; Arnault Tauziede‐Espariat; Marc Zanello; Albane Gareton; Edouard Dezamis; Frédéric Dhermain; Fabrice Chretien; Emmanuèle Lechapt‐Zalcman; Catherine Oppenheim; Johan Pallud; Pascale Varlet
Assess the contribution of preoperative MRI data in improving grading of adult astrocytomas reclassified according to the WHO 2016 and cIMPACT‐NOW update 3.
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The microbiota–microglia axis in central nervous system disorders Brain Pathol. (IF 5.568) Pub Date : 2020-10-19 Omar Mossad; Daniel Erny
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The use and limitations of single‐cell mass cytometry for studying human microglia function Brain Pathol. (IF 5.568) Pub Date : 2020-10-15 Camila Fernández‐Zapata; Julia K. H. Leman; Josef Priller; Chotima Böttcher
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Deciphering the heterogeneity of myeloid cells during neuroinflammation in the single‐cell era Brain Pathol. (IF 5.568) Pub Date : 2020-10-15 Katharina Borst; Marco Prinz
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Interaction of microglia with infiltrating immune cells in the different phases of stroke Brain Pathol. (IF 5.568) Pub Date : 2020-10-15 Daniel Berchtold; Josef Priller; Christian Meisel; Andreas Meisel
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Tumor cell and immune cell profiles in primary human glioblastoma: Impact on patient outcome Brain Pathol. (IF 5.568) Pub Date : 2020-12-14 María González‐Tablas; Álvaro Otero; Daniel Arandia; Daniel Pascual; Laura Ruiz; Pablo Sousa; Andoni García; Juan Carlos Roa; Jorge Javier MD Villaseñor; Luis Torres; Maria do Rosário Almeida; Javier Pedro Ortiz; Adelaida Nieto; Alberto Orfao; María Dolores Tabernero
The distribution and role of tumor infiltrating leucocytes in glioblastoma (GBM) remain largely unknown. Here, we investigated the cellular composition of 55 primary (adult) GBM samples by flowcytometry and correlated the tumor immune profile with patient features at diagnosis and outcome.
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A novel temporal‐predominant neuro‐astroglial tauopathy associated with TMEM106B gene polymorphism in FTLD/ALS‐TDP Brain Pathol. (IF 5.568) Pub Date : 2020-12-12 Jorge J Llibre‐Guerra; Suzee E. Lee; Claudia K Suemoto; Alexander J. Ehrenberg; Gabor G. Kovacs; Anna Karydas; Adam Staffaroni; Elisa De Paula Franca Resende; Eun‐Joo Kim; Ji‐Hye Hwang; Eliana Marisa Ramos; Kevin J. Wojta; Lorenzo Pasquini; Shirley Yin‐Yu Pang; Salvatore Spina; Isabel E. Allen; Joel Kramer; Bruce L. Miller; William W. Seeley; Lea T. Grinberg
Polymorphisms in TMEM106B, a gene on chromosome 7p21.3 involved in lysosomal trafficking, correlates to worse neuropathological and clinical outcomes in frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) with TDP‐43 inclusions. In a small cohort of C9orf72 expansion carriers, we previously found an atypical, neuroglial tauopathy in cases harboring a TMEM106B rs1990622
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Downregulated GPR30 Expression in the Epileptogenic Foci of Female Patients with Focal Cortical Dysplasia Type IIb and Tuberous Sclerosis Complex Is Correlated with 18F‐FDG PET‐CT Values Brain Pathol. (IF 5.568) Pub Date : 2020-12-12 Zhongke Wang; Kaixuan Huang; Xiaolin Yang; Kaifeng Shen; Ling Yang; Ruotong Ruan; Xianjun Shi; Miao Wang; Gang Zhu; Meihua Yang; Chunqing Zhang; Shengqing Lv; Hui Yang; Xiaotang Fan; Shiyong Liu
Focal cortical dysplasia type IIb (FCDIIb) and tuberous sclerosis complex (TSC) are typical causes of developmental delay and refractory epilepsy. G‐protein‐coupled receptor 30 (GPR30) is a specific estrogen receptor that is critical in neurodevelopment, neuroinflammation, and neuronal excitability, suggesting that it plays a potential role in the epilepsy of patients with FCDIIb and TSC. Therefore
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Detection and Quantification of Novel C‐terminal TDP‐43 Fragments in ALS‐TDP Brain Pathol. (IF 5.568) Pub Date : 2020-12-10 Emily Feneberg; Philip D. Charles; Mattéa J. Finelli; Connor Scott; Benedikt M. Kessler; Roman Fischer; Olaf Ansorge; Elizabeth Gray; Kevin Talbot; Martin R. Turner
The pathological hallmark of amyotrophic lateral sclerosis (ALS) is the presence of cytoplasmic inclusions, containing C‐terminal fragments of the protein TDP‐43. Here, we tested the hypothesis that highly sensitive mass spectrometry with parallel reaction monitoring (MS‐PRM) can generate a high‐resolution map of pathological TDP‐43 peptide ratios to form the basis for quantitation of abnormal C‐terminal
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Distinct circular RNA expression profiles in pediatric ependymomas Brain Pathol. (IF 5.568) Pub Date : 2020-11-28 Ulvi Ahmadov; Meile M. Bendikas; Karoline K. Ebbesen; Astrid M. Sehested; Jørgen Kjems; Helle Broholm; Lasse S. Kristensen
Pediatric ependymomas frequently develop in the cerebellum and are currently treated using non‐specific therapies, in part, because few somatically mutated driver genes are present, and the underlying pathobiology is poorly described. Circular RNAs (circRNAs) constitute as a large class of primarily non‐coding RNAs with important roles in tumorigenesis, but they have not been described in pediatric
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The presence of TIM‐3 positive cells in WHO grade III and IV astrocytic gliomas correlates with isocitrate dehydrogenase mutation status Brain Pathol. (IF 5.568) Pub Date : 2020-11-26 Mia D. Sørensen; Ole Nielsen; Guido Reifenberger; Bjarne W. Kristensen
Diffuse gliomas are aggressive brain tumors that respond poorly to immunotherapy including immune checkpoint inhibition. This resistance may arise from an immunocompromised microenvironment and deficient immune recognition of tumor cells due to low mutational burden. The most prominent genetic alterations in diffuse glioma are mutations in the isocitrate dehydrogenase (IDH) genes that generate the
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Iron accumulation in the choroid plexus, ependymal cells and CNS parenchyma in a rat strain with low‐grade haemolysis of fragile macrocytic red blood cells Brain Pathol. (IF 5.568) Pub Date : 2020-11-21 Isabella Wimmer; Cornelia Scharler; Taro Kadowaki; Sophie Hillebrand; Barbara Scheiber‐Mojdehkar; Shuichi Ueda; Monika Bradl; Thomas Berger; Hans Lassmann; Simon Hametner
Iron accumulation in the CNS is associated with many neurological diseases via amplification of inflammation and neurodegeneration. However, experimental studies on iron overload are challenging, since rodents hardly accumulate brain iron contrary to humans. Here, we studied LEWzizi rats, which present with elevated CNS iron loads, aiming to characterize choroid plexus, ependymal, CSF and CNS parenchymal
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Overexpression of the ubiquitin‐editing enzyme A20 in the brain lesions of Multiple Sclerosis patients: moving from systemic to central nervous system inflammation Brain Pathol. (IF 5.568) Pub Date : 2020-10-14 Simona Perga; Francesca Montarolo; Serena Martire; Brigitta Bonaldo; Gabriele Bono; Jessica Bertolo; Roberta Magliozzi; Antonio Bertolotto
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The spectrum of rare central nervous system (CNS) tumors with EWSR1‐non‐ETS fusions: experience from three pediatric institutions with review of the literature Brain Pathol. (IF 5.568) Pub Date : 2020-09-30 Oscar Lopez‐Nunez; Barbara Cafferata; Mariarita Santi; Sarangarajan Ranganathan; Thomas M. Pearce; Scott M. Kulich; Kelly M. Bailey; Alberto Broniscer; Sabrina Rossi; Angelica Zin; MacLean P. Nasrallah; Marilyn M. Li; Yiming Zhong; Evelina Miele; Rita Alaggio; Lea F. Surrey
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Accumulation of neurofibrillary tangles and activated microglia is associated with lower neuron densities in the aphasic variant of Alzheimer’s disease Brain Pathol. (IF 5.568) Pub Date : 2020-10-03 Daniel T. Ohm; Angela J. Fought; Adam Martersteck; Christina Coventry; Jaiashre Sridhar; Tamar Gefen; Sandra Weintraub; Eileen Bigio; M.‐Marsel Mesulam; Emily Rogalski; Changiz Geula
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Intracranial mesenchymal tumor with FET‐CREB fusion – a unifying diagnosis for the spectrum of intracranial myxoid mesenchymal tumors and angiomatoid fibrous histiocytoma‐like neoplasms Brain Pathol. (IF 5.568) Pub Date : 2020-11-03 Emily A. Sloan; Jason Chiang; Javier E. Villanueva‐Meyer; Sanda Alexandrescu; Jennifer M. Eschbacher; Wesley Wang; Manuela Mafra; Nassir Ud Din; Emily Carr‐Boyd; Michael Watson; Michael Punsoni; Angelica Oviedo; Ahmed Gilani; Bette K. Kleinschmidt‐DeMasters; Dylan J. Coss; M. Beatriz Lopes; Corey Raffel; Mitchel S. Berger; Susan Chang; Alyssa Reddy; Biswarathan Ramani; Sean P. Ferris; Julieann C. Lee;
Intracranial mesenchymal tumors with FET‐CREB fusions are a recently described group of neoplasms in children and young adults characterized by fusion of a FET family gene (usually EWSR1, but rarely FUS) to a CREB family transcription factor (ATF1, CREB1, or CREM), and have been variously termed intracranial angiomatoid fibrous histiocytoma or intracranial myxoid mesenchymal tumor. The clinical outcomes
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Cerebellar developmental deficits underlie neurodegenerative disorder spinocerebellar ataxia type 23 Brain Pathol. (IF 5.568) Pub Date : 2020-10-12 Cleo J.L.M. Smeets; Kai Yu Ma; Simon E. Fisher; Dineke S. Verbeek
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Low‐grade BRAF V600E mutant oligodendroglioma‐like tumors of children may show EGFR and MET amplification Brain Pathol. (IF 5.568) Pub Date : 2020-10-08 Rui Ryan Yang; Kay Ka‐Wai Li; Anthony P.Y. Liu; Hong Chen; Nellie Yuk‐Fei Chung; Aden K.Y. Chan; Fangcheng Li; Danny Tat‐Ming Chan; Ying Mao; Zhi‐Feng Shi; Ho‐Keung Ng
Pediatric low‐grade gliomas were shown to be characterized by an array of distinct molecular aberrations. The recent cIMPACT‐4 consensus proposed pediatric low‐grade gliomas of the diffuse type to be characterized by distinct molecular changes rather than distinct histological features (2). Very recently, Fukuoka et al described a small series of pediatric oligodendroglioma‐like tumors with BRAF V600E
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Brain ischemic injury in COVID‐19‐infected patients: a series of 10 post‐mortem cases Brain Pathol. (IF 5.568) Pub Date : 2020-10-01 Viscardo P. Fabbri; Maria P. Foschini; Tiziana Lazzarotto; Liliana Gabrielli; Giovanna Cenacchi; Carmine Gallo; Raffaele Aspide; Guido Frascaroli; Pietro Cortelli; Mattia Riefolo; Caterina Giannini; Antonietta D'Errico
To the Editor: The coronavirus disease 2019 (COVID‐19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). COVID‐19 symptoms are not limited to the respiratory tract, but complications have been described involving other organs including brain. At present, data on SARS‐CoV‐2 neuropathological features are limited (4, 5, 8, 10) and most frequently focused on cases presenting
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Isoform‐specific upregulation of FynT kinase expression is associated with tauopathy and glial activation in Alzheimer’s disease and Lewy body dementias Brain Pathol. (IF 5.568) Pub Date : 2020-10-31 Clara Y.B. Low; Jasinda H. Lee; Frances T.W. Lim; Chingli Lee; Clive Ballard; Paul T. Francis; Mitchell K.P. Lai; Michelle G.K. Tan
Cumulative data suggest the involvement of Fyn tyrosine kinase in Alzheimer's disease (AD). Previously, our group has shown increased immunoreactivities of the FynT isoform in AD neocortex (with no change in the alternatively spliced FynB isoform) which associated with neurofibrillary degeneration and reactive astrogliosis. Since both the aforementioned neuropathological features are also variably
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Aged Tmem106b knockout mice display gait deficits in coincidence with Purkinje cell loss and only limited signs of non‐motor dysfunction Brain Pathol. (IF 5.568) Pub Date : 2020-10-05 Stijn Stroobants; Rudi D’Hooge; Markus Damme
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The myeloid side of the CNS Brain Pathol. (IF 5.568) Pub Date : 2020-10-16 Anaelle A Dumas; Marco Prinz
Microglia are known as the tissue‐resident macrophages of the central nervous system (CNS). Yet their unique ontogeny and distinguishing features endowed by the privileged nature of their environment have set them apart from other myeloid cells in the body. Microglia spectrum of activity enables their participation in the maintenance of homeostasis and disease processes via their interaction with CNS
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Role of mTOR-regulated autophagy in spine pruning defects and memory impairments induced by binge-like ethanol treatment in adolescent mice. Brain Pathol. (IF 5.568) Pub Date : 2020-09-02 María Pascual,Rosa López-Hidalgo,Sandra Montagud-Romero,Juan R Ureña-Peralta,Marta Rodríguez-Arias,Consuelo Guerri
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Unfolded protein response activation in C9orf72 frontotemporal dementia is associated with dipeptide pathology and granulovacuolar degeneration in granule cells. Brain Pathol. (IF 5.568) Pub Date : 2020-08-31 Priya Gami-Patel,Irene van Dijken,Lieke H Meeter,Shamiram Melhem,Tjado H J Morrema,Wiep Scheper,John C van Swieten,Annemieke J M Rozemuller,Anke A Dijkstra,Jeroen J M Hoozemans
A repeat expansion in the C9orf72 gene is the most prevalent genetic cause of frontotemporal dementia (C9‐FTD). Several studies have indicated the involvement of the unfolded protein response (UPR) in C9‐FTD. In human neuropathology, UPR markers are strongly associated with granulovacuolar degeneration (GVD). In this study, we aim to assess the presence of UPR markers together with the presence of
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TERT promoter mutations in primary and secondary WHO grade III meningioma. Brain Pathol. (IF 5.568) Pub Date : 2020-08-17 Andrea Daniela Maier,Adam Stenman,Fredrika Svahn,Christian Mirian,Jiri Bartek,Marianne Juhler,Jan Zedenius,Helle Broholm,Tiit Mathiesen
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Distribution of tau hyperphosphorylation in canine dementia resembles early Alzheimer's disease and other tauopathies. Brain Pathol. (IF 5.568) Pub Date : 2020-08-18 Ajantha Abey,Danielle Davies,Claire Goldsbury,Michael Buckland,Michael Valenzuela,Thomas Duncan
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Medullary tyrosine hydroxylase catecholaminergic neuronal populations in sudden unexpected death in epilepsy. Brain Pathol. (IF 5.568) Pub Date : 2020-08-15 Smriti Patodia,Ian Tan,Matthew Ellis,Alyma Somani,Ingrid E Scheffer,Sanjay Sisodiya,Maria Thom
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Distinct microglial and macrophage distribution patterns in the concentric and lamellar lesions in Baló's disease and neuromyelitis optica spectrum disorders. Brain Pathol. (IF 5.568) Pub Date : 2020-09-09 Shotaro Hayashida,Katsuhisa Masaki,Satoshi O Suzuki,Ryo Yamasaki,Mitsuru Watanabe,Sachiko Koyama,Noriko Isobe,Takuya Matsushita,Kazuya Takahashi,Takeshi Tabira,Toru Iwaki,Jun-Ichi Kira
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The molecular etiology of Alzheimer's disease. Brain Pathol. (IF 5.568) Pub Date : 2020-07-12 Adam R Smith,Jonathan Mill,Katie Lunnon
Alzheimer’s disease (AD) is a growing global healthcare epidemic. Owing to advances in technology, genome‐scale studies of various layers of molecular information have been undertaken in recent years and robust variation in key loci have now been published and reproduced by others. This mini‐symposium highlights four key areas of current research in the field of molecular biology in AD, including articles
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Genomic mechanisms in Alzheimer's disease. Brain Pathol. (IF 5.568) Pub Date : 2020-07-13 Lars Bertram,Rudolph E Tanzi
Alzheimer's disease (AD) is the most common neurodegenerative disease and, owing to its increasing prevalence, represents one of the leading public health problems in aging populations. The molecular causes underlying the onset and progression of AD are manifold and hitherto still incompletely understood. Research over nearly four decades has clearly delineated genetics to play a crucial role in AD
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Epigenome-wide association studies in Alzheimer's disease; achievements and challenges. Brain Pathol. (IF 5.568) Pub Date : 2020-07-12 Daniel L A van den Hove,Renzo J M Riemens,Philippos Koulousakis,Ehsan Pishva
Alzheimer’s disease (AD) represents a devastating progressive neurodegenerative disease with a complex pathophysiology, affecting millions of people worldwide. Recent epigenome‐wide association studies suggest a key role for epigenetic mechanisms in its development and course. Despite the fact that current evidence on the role of epigenetic dysregulation in aging and AD is convincing, the pioneering
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Considerations for integrative multi-omic approaches to explore Alzheimer's disease mechanisms. Brain Pathol. (IF 5.568) Pub Date : 2020-07-12 Yiyi Ma,Hans-Ulrich Klein,Philip L De Jager
The past decade has seen the maturation of multiple different forms of high‐dimensional molecular profiling to the point that these methods could be deployed in initially hundreds and more recently thousands of human samples. In the field of Alzheimer's disease (AD), these profiles have been applied to the target organ: the aging brain. In a growing number of cases, the same samples were profiled with
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Applying gene-editing technology to elucidate the functional consequence of genetic and epigenetic variation in Alzheimer's disease. Brain Pathol. (IF 5.568) Pub Date : 2020-07-12 Michael Schrauben,Emma Dempster,Katie Lunnon
Recent studies have highlighted a potential role of genetic and epigenetic variation in the development of Alzheimer’s disease. Application of the CRISPR‐Cas genome‐editing platform has enabled investigation of the functional impact that Alzheimer’s disease‐associated gene mutations have on gene expression. Moreover, recent advances in the technology have led to the generation of CRISPR‐Cas–based tools
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Denser brain capillary network with preserved pericytes in alzheimer's disease. Brain Pathol. (IF 5.568) Pub Date : 2020-09-02 Francisco Fernandez-Klett,Lasse Brandt,Camila Fernández-Zapata,Basim Abuelnor,Jinte Middeldorp,Jacqueline A Sluijs,Maurice Curtis,Richard Faull,Laura W Harris,Sabine Bahn,Elly Hol,Josef Priller
Pericytes are vascular mural cells that surround capillaries of the central nervous system (CNS). They are crucial for brain development and contribute to CNS homeostasis by regulating blood–brain barrier function and cerebral blood flow. It has been suggested that pericytes are lost in Alzheimer's disease (AD), implicating this cell type in disease pathology. Here, we have employed state‐of‐the‐art
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Distinct changes in all major components of the neurovascular unit across different neuropathological stages of Alzheimer's disease. Brain Pathol. (IF 5.568) Pub Date : 2020-08-31 Tunahan Kirabali,Ruslan Rust,Serena Rigotti,Alessandro Siccoli,Roger M Nitsch,Luka Kulic
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RAB39B is redistributed in dementia with Lewy bodies and is sequestered within aβ plaques and Lewy bodies. Brain Pathol. (IF 5.568) Pub Date : 2020-08-06 David J Koss,Odeta Bondarevaite,Sara Adams,Marta Leite,Flaviano Giorgini,Johannes Attems,Tiago F Outeiro
Loss of function mutations within the vesicular trafficking protein Ras analogy in brain 39B (RAB39B) are associated with rare X‐linked Parkinson’s disease (PD). Physiologically, RAB39B is localized to Golgi vesicles and recycling endosomes and is required for glutamatergic receptor maturation but also for alpha‐Synuclein (aSyn) homeostasis and the inhibition of its aggregation. Despite evidence linking
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PKR kinase directly regulates tau expression and Alzheimer's disease-related tau phosphorylation. Brain Pathol. (IF 5.568) Pub Date : 2020-07-27 Lasse Reimer,Cristine Betzer,Rikke Hahn Kofoed,Christiane Volbracht,Karina Fog,Chaitanya Kurhade,Emma Nilsson,Anna K Överby,Poul Henning Jensen
Deposition of extensively hyperphosphorylated tau in specific brain cells is a clear pathological hallmark in Alzheimer's disease and a number of other neurodegenerative disorders, collectively termed the tauopathies. Furthermore, hyperphosphorylation of tau prevents it from fulfilling its physiological role as a microtubule‐stabilizing protein and leaves it increasingly vulnerable to self‐assembly
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Neuropathologic features of four autopsied COVID-19 patients. Brain Pathol. (IF 5.568) Pub Date : 2020-08-06 Jonas Kantonen,Shamita Mahzabin,Mikko I Mäyränpää,Olli Tynninen,Anders Paetau,Noora Andersson,Antti Sajantila,Olli Vapalahti,Olli Carpén,Eliisa Kekäläinen,Anu Kantele,Liisa Myllykangas
Introduction Many symptoms of COVID‐19, such as stroke, anosmia and dysregulation of breathing are considered to be directly or partly attributable to neuropathological processes (4). Furthermore, severe radiologically verified manifestations, such as acute hemorrhagic necrotizing encephalitis (AHLE) and acute disseminated encephalomyelitis (ADEM) have been reported (5). Here, we present neuropathological
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Congenital tumors of the central nervous system: an institutional review of 64 cases with emphasis on tumors with unique histologic and molecular characteristics. Brain Pathol. (IF 5.568) Pub Date : 2020-07-17 Angela N Viaene,Cunfeng Pu,Arie Perry,Marilyn M Li,Minjie Luo,Mariarita Santi
Congenital brain tumors are rare accounting for 0.5%–1.9% of all pediatric brain tumors. While different criteria have been used to classify a tumor as congenital, those diagnosed prior to 6 months of age are considered to be “probably” congenital in origin. We performed an institutional review of all central nervous system (CNS) tumors (surgical and autopsy specimens from 1990 to 2019) in patients
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Neonatal apneic phenotype in a murine congenital central hypoventilation syndrome model is induced through non-cell autonomous developmental mechanisms. Brain Pathol. (IF 5.568) Pub Date : 2020-07-12 Diego Alzate-Correa,Jillian Mei-Ling Liu,Mikayla Jones,Talita M Silva,Michele Joana Alves,Elizabeth Burke,Jessica Zuñiga,Behiye Kaya,Giuliana Zaza,Mehmet Tahir Aslan,Jessica Blackburn,Marina Y Shimada,Silvio A Fernandes-Junior,Lisa A Baer,Kristin I Stanford,Amber Kempton,Sakima Smith,Caroline C Szujewski,Abby Silbaugh,Jean-Charles Viemari,Ana C Takakura,Alfredo J Garcia,Thiago S Moreira,Catherine M
Congenital central hypoventilation syndrome (CCHS) represents a rare genetic disorder usually caused by mutations in the homeodomain transcription factor PHOX2B . Some CCHS patients suffer mainly from deficiencies in CO2 and/or O2 respiratory chemoreflex, whereas other patients present with full apnea shortly after birth. Our goal was to identify the neuropathological mechanisms of apneic presentations
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Biology and grading of pleomorphic xanthoastrocytoma-what have we learned about it? Brain Pathol. (IF 5.568) Pub Date : 2020-07-03 Rachael Vaubel,Valentina Zschernack,Quynh T Tran,Sarah Jenkins,Alissa Caron,Dragana Milosevic,James Smadbeck,George Vasmatzis,Daniela Kandels,Astrid Gnekow,Christof Kramm,Robert Jenkins,Benjamin R Kipp,Fausto J Rodriguez,Brent A Orr,Torsten Pietsch,Caterina Giannini
Pleomorphic xanthoastrocytoma (PXA) is a rare astrocytoma predominantly affecting children and young adults. We performed comprehensive genomic characterization on a cohort of 67 patients with histologically defined PXA (n = 53, 79%) or anaplastic PXA (A‐PXA, n = 14, 21%), including copy number analysis (ThermoFisher Oncoscan, n = 67), methylation profiling (Illumina EPIC array, n = 43) and targeted
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Ependymoma relapse goes along with a relatively stable epigenome, but a severely altered tumor morphology. Brain Pathol. (IF 5.568) Pub Date : 2020-07-06 Denise Yang,Till Holsten,Daniela Börnigen,Stephan Frank,Christian Mawrin,Markus Glatzel,Ulrich Schüller
The molecular biology of ependymomas is not well understood and this is particularly true for ependymoma relapses. We aimed at finding out if and to which extent, relapses differ from their corresponding primary tumors on the morphological, chromosomal and epigenetic level. We investigated 24 matched ependymoma primary and relapsed tumor samples and, as a first step, compared cell density, necrosis
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Pediatric meningioma: a clinicopathologic and molecular study with potential grading implications. Brain Pathol. (IF 5.568) Pub Date : 2020-07-27 Angus Toland,Samantha N McNulty,Melike Pekmezci,Michael Evenson,Kristin Huntoon,Christopher R Pierson,Daniel R Boue,Arie Perry,Sonika Dahiya
Meningiomas are common in adults (~35% of brain tumors) but rare in children, where they exhibit unique clinical, pathological and molecular features compared to adult counterparts. Thus, data generated from adult cohorts may be imperfectly suited to guiding diagnostic, prognostic and treatment decisions for children. We studied 50 meningioma patients ≤18 years with available clinical and pathological
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Loss of capillary pericytes and the blood-brain barrier in white matter in poststroke and vascular dementias and Alzheimer's disease. Brain Pathol. (IF 5.568) Pub Date : 2020-07-23 Ren Ding,Yoshiki Hase,Kamar E Ameen-Ali,Michael Ndung'u,William Stevenson,Joseph Barsby,Ryan Gourlay,Tolulope Akinyemi,Rufus Akinyemi,Maiko T Uemura,Tuomo Polvikoski,Elizabeta Mukaetova-Ladinska,Masafumi Ihara,Raj N Kalaria
White matter (WM) disease is associated with disruption of the gliovascular unit, which involves breach of the blood–brain barrier (BBB). We quantified pericytes as components of the gliovascular unit and assessed their status in vascular and other common dementias. Immunohistochemical and immunofluorescent methods were developed to assess the distribution and quantification of pericytes connected
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Epithelioid glioblastoma with microglia features: potential for novel therapy. Brain Pathol. (IF 5.568) Pub Date : 2020-07-20 Nami Nakagomi,Daisuke Sakamoto,Takanori Hirose,Toshinori Takagi,Makiko Murase,Takayuki Nakagomi,Shinichi Yoshimura,Seiichi Hirota
Epithelioid glioblastoma (E‐GBM) was recently designated as a subtype of glioblastoma (GBM) by the World Health Organization (2016). E‐GBM is an aggressive and rare variant of GBM that primarily occurs in children and young adults. Although most characterized cases of E‐GBM harbor a mutation of the BRAF gene in which valine (V) is substituted by glutamic acid (E) at amino acid 600 (BRAF‐V600E), in
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IL-1β/IL-1R1 signaling induced by intranasal lipopolysaccharide infusion regulates alpha-synuclein pathology in the olfactory bulb, substantia nigra and striatum. Brain Pathol. (IF 5.568) Pub Date : 2020-07-17 Haichen Niu,Qian Wang,Weiguang Zhao,Jianxin Liu,Deguang Wang,Bilal Muhammad,Xiaoyu Liu,Ning Quan,Haoyu Zhang,Fang Zhang,Yong Wang,Haiying Li,Rongli Yang
Olfactory dysfunction is one of the early symptoms seen in Parkinson’s disease (PD). However, the mechanisms underlying olfactory pathology that impacts PD disease progression and post‐mortem appearance of alpha‐Synuclein (α‐Syn) inclusions in and beyond olfactory bulb in PD remain unclear. It has been suggested that environmental toxins inhaled through the nose can induce inflammation in the olfactory
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Neuropathological profile of long-duration amyotrophic lateral sclerosis in military Veterans. Brain Pathol. (IF 5.568) Pub Date : 2020-07-07 Keith R Spencer,Zachariah W Foster,Nazifa Abdul Rauf,Latease Guilderson,Derek Collins,James G Averill,Sean E Walker,Ian Robey,Jonathan D Cherry,Victor E Alvarez,Bertrand R Huber,Ann C McKee,Neil W Kowall,Christopher B Brady,Thor D Stein
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting both the upper and lower motor neurons. Although ALS typically leads to death within 3 to 5 years after initial symptom onset, approximately 10% of patients with ALS live more than 10 years after symptom onset. We set out to determine similarities and differences in clinical presentation and neuropathology in
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Detection of endophenotypes associated with neuropsychiatric deficiencies in a mouse model of tuberous sclerosis complex using diffusion tensor imaging. Brain Pathol. (IF 5.568) Pub Date : 2020-06-12 Christine Chin-Jung Hsieh,Yu-Chun Lo,Ssu-Ju Li,Ting-Chun Lin,Ching-Wen Chang,Ting-Chieh Chen,Shih-Hung Yang,Yi-Chao Lee,You-Yin Chen
Tuberous sclerosis complex (TSC) is a rare hereditary disease, which results from the mutation of either TSC1 or TSC2 , and its clinical features include benign tumors and dysfunctions in numerous organs, including the brain. Many individuals with TSC manifest neuropsychiatric symptoms, such as learning impairments, cognitive deficits and anxiety. Current pharmacological treatment for TSC is the use
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Investigating the presence of doubly phosphorylated α-synuclein at tyrosine 125 and serine 129 in idiopathic Lewy body diseases. Brain Pathol. (IF 5.568) Pub Date : 2020-04-23 Muneera Fayyad,Daniel Erskine,Nour K Majbour,Nishant N Vaikath,Simona S Ghanem,Indulekha P Sudhakaran,Houari Abdesselem,Agaristi Lamprokostopoulou,Kostas Vekrellis,Christopher M Morris,Johannes Attems,Omar M A El-Agnaf
Aggregation of the protein α‐synuclein (α‐syn) into insoluble intracellular assemblies termed Lewy bodies (LBs) is thought to be a critical pathogenic event in LB diseases such as Parkinson’s disease and dementia with LBs. In LB diseases, the majority of α‐syn is phosphorylated at serine 129 (pS129), suggesting that this is an important disease‐related post‐translational modification (PTM). However
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cIMPACT‐NOW update 6: new entity and diagnostic principle recommendations of the cIMPACT‐Utrecht meeting on future CNS tumor classification and grading Brain Pathol. (IF 5.568) Pub Date : 2020-04-19 David N. Louis; Pieter Wesseling; Kenneth Aldape; Daniel J. Brat; David Capper; Ian A. Cree; Charles Eberhart; Dominique Figarella‐Branger; Maryam Fouladi; Gregory N. Fuller; Caterina Giannini; Christine Haberler; Cynthia Hawkins; Takashi Komori; Johan M. Kros; HK Ng; Brent A. Orr; Sung‐Hye Park; Werner Paulus; Arie Perry; Torsten Pietsch; Guido Reifenberger; Marc Rosenblum; Brian Rous; Felix Sahm;
cIMPACT‐NOW (the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy) was established to evaluate and make practical recommendations on recent advances in the field of CNS tumor classification, particularly in light of the rapid progress in molecular insights into these neoplasms. For Round 2 of its deliberations, cIMPACT‐NOW Working Committee 3 was reconstituted and convened