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Acta Neuropathologica

Jinping Cheng, Nils Korte, Ross Nortley, Huma Sethi, Yamei Tang, David Attwell
Many central nervous system diseases currently lack effective treatment and are often associated with defects in microvascular function, including a failure to match the energy supplied by the blood to the energy used on neuronal computation, or a breakdown of the blood-brain barrier. Pericytes, an under-studied cell type located on capillaries, are of crucial importance in regulating diverse microvascular functions, such as angiogenesis, the blood-brain barrier, capillary blood flow and the movement of immune cells into the brain...
August 10, 2018: Acta Neuropathologica
David Capper, Nils W Engel, Damian Stichel, Matt Lechner, Stefanie Glöss, Simone Schmid, Christian Kölsche, Daniel Schrimpf, Judith Niesen, Annika K Wefers, David T W Jones, Martin Sill, Oliver Weigert, Keith L Ligon, Adriana Olar, Arend Koch, Martin Forster, Sebastian Moran, Oscar M Tirado, Miguel Sáinz-Jaspeado, Jaume Mora, Manel Esteller, Javier Alonso, Xavier Garcia Del Muro, Werner Paulus, Jörg Felsberg, Guido Reifenberger, Markus Glatzel, Stephan Frank, Camelia M Monoranu, Valerie J Lund, Andreas von Deimling, Stefan Pfister, Rolf Buslei, Julika Ribbat-Idel, Sven Perner, Volker Gudziol, Matthias Meinhardt, Ulrich Schüller
In the original publication, the second name of the twentieth author was incorrect. It should read as 'Miguel Sáinz-Jaspeado'. The original publication of the article has been updated to reflect the change. This correction was authored by Ulrich Schüller on behalf of all authors of the original publication.
August 9, 2018: Acta Neuropathologica
Kurt A Jellinger
No abstract text is available yet for this article.
August 7, 2018: Acta Neuropathologica
Jun Wang, Wang-Sheng Jin, Xian-Le Bu, Fan Zeng, Zhi-Lin Huang, Wei-Wei Li, Lin-Lin Shen, Zhen-Qian Zhuang, Yuqiang Fang, Bin-Lu Sun, Jie Zhu, Xiu-Qing Yao, Gui-Hua Zeng, Zhi-Fang Dong, Jin-Tai Yu, Zhian Hu, Weihong Song, Hua-Dong Zhou, Jian-Xin Jiang, Yu-Hui Liu, Yan-Jiang Wang
Accumulation of pathological tau is the hallmark of Alzheimer's disease and other tauopathies and is closely correlated with cognitive decline. Clearance of pathological tau from the brain is a major therapeutic strategy for tauopathies. The physiological capacity of the periphery to clear brain-derived tau and its therapeutic potential remain largely unknown. Here, we found that cisterna magna injected 131 I-labelled synthetic tau dynamically effluxed from the brain and was mainly cleared from the kidney, blood, and liver in mice; we also found that plasma tau levels in inferior vena cava were lower than those in femoral artery in humans...
August 3, 2018: Acta Neuropathologica
Gaia Faustini, Francesca Longhena, Tatiana Varanita, Luigi Bubacco, Marina Pizzi, Cristina Missale, Fabio Benfenati, Anders Björklund, PierFranco Spano, Arianna Bellucci
Parkinson's disease (PD), the most common neurodegenerative movement disorder, is characterized by the progressive loss of nigral dopamine neurons. The deposition of fibrillary aggregated α-synuclein in Lewy bodies (LB), that is considered to play a causative role in the disease, constitutes another key neuropathological hallmark of PD. We have recently described that synapsin III (Syn III), a synaptic phosphoprotein that regulates dopamine release in cooperation with α-synuclein, is present in the α-synuclein insoluble fibrils composing the LB of patients affected by PD...
July 25, 2018: Acta Neuropathologica
Helmut Heinsen, Lea T Grinberg
No abstract text is available yet for this article.
July 23, 2018: Acta Neuropathologica
Rebeka Fekete, Csaba Cserép, Nikolett Lénárt, Krisztina Tóth, Barbara Orsolits, Bernadett Martinecz, Előd Méhes, Bálint Szabó, Valéria Németh, Balázs Gönci, Beáta Sperlágh, Zsolt Boldogkői, Ágnes Kittel, Mária Baranyi, Szilamér Ferenczi, Krisztina Kovács, Gergely Szalay, Balázs Rózsa, Connor Webb, Gabor G Kovacs, Tibor Hortobágyi, Brian L West, Zsuzsanna Környei, Ádám Dénes
Neurotropic herpesviruses can establish lifelong infection in humans and contribute to severe diseases including encephalitis and neurodegeneration. However, the mechanisms through which the brain's immune system recognizes and controls viral infections propagating across synaptically linked neuronal circuits have remained unclear. Using a well-established model of alphaherpesvirus infection that reaches the brain exclusively via retrograde transsynaptic spread from the periphery, and in vivo two-photon imaging combined with high resolution microscopy, we show that microglia are recruited to and isolate infected neurons within hours...
July 19, 2018: Acta Neuropathologica
David A Solomon, Andrey Korshunov, Martin Sill, David T W Jones, Marcel Kool, Stefan M Pfister, Xuemo Fan, Serguei Bannykh, Jethro Hu, Moise Danielpour, Rong Li, James Johnston, Elaine Cham, Tabitha Cooney, Peter P Sun, Nancy Ann Oberheim Bush, Michael McDermott, Jessica Van Ziffle, Courtney Onodera, James P Grenert, Boris C Bastian, Javier E Villanueva-Meyer, Melike Pekmezci, Andrew W Bollen, Arie Perry
No abstract text is available yet for this article.
July 13, 2018: Acta Neuropathologica
Shahzad S Khan, Michael LaCroix, Gabriel Boyle, Mathew A Sherman, Jennifer L Brown, Fatou Amar, Jacqeline Aldaco, Michael K Lee, George S Bloom, Sylvain E Lesné
α-Synuclein (αSyn) histopathology defines several neurodegenerative disorders, including Parkinson's disease, Lewy body dementia, and Alzheimer's disease (AD). However, the functional link between soluble αSyn and disease etiology remains elusive, especially in AD. We, therefore, genetically targeted αSyn in APP transgenic mice modeling AD and mouse primary neurons. Our results demonstrate bidirectional modulation of behavioral deficits and pathophysiology by αSyn. Overexpression of human wild-type αSyn in APP animals markedly reduced amyloid deposition but, counter-intuitively, exacerbated deficits in spatial memory...
July 11, 2018: Acta Neuropathologica
Rachid El Fatimy, Shaomin Li, Zhicheng Chen, Tasnim Mushannen, Sree Gongala, Zhiyun Wei, Darrick T Balu, Rosalia Rabinovsky, Adam Cantlon, Abdallah Elkhal, Dennis J Selkoe, Kai C Sonntag, Dominic M Walsh, Anna M Krichevsky
MicroRNAs (miRNA) regulate fundamental biological processes, including neuronal plasticity, stress response, and survival. Here, we describe a neuroprotective function of miR-132, the miRNA most significantly downregulated in neurons in Alzheimer's disease. We demonstrate that miR-132 protects primary mouse and human wild-type neurons and more vulnerable Tau-mutant neurons against amyloid β-peptide (Aβ) and glutamate excitotoxicity. It lowers the levels of total, phosphorylated, acetylated, and cleaved forms of Tau implicated in tauopathies, promotes neurite elongation and branching, and reduces neuronal death...
July 7, 2018: Acta Neuropathologica
Yuetiva Deming, Logan Dumitrescu, Lisa L Barnes, Madhav Thambisetty, Brian Kunkle, Katherine A Gifford, William S Bush, Lori B Chibnik, Shubhabrata Mukherjee, Philip L De Jager, Walter Kukull, Matt Huentelman, Paul K Crane, Susan M Resnick, C Dirk Keene, Thomas J Montine, Gerard D Schellenberg, Jonathan L Haines, Henrik Zetterberg, Kaj Blennow, Eric B Larson, Sterling C Johnson, Marilyn Albert, Abhay Moghekar, Jorge L Del Aguila, Maria Victoria Fernandez, John Budde, Jason Hassenstab, Anne M Fagan, Matthias Riemenschneider, Ronald C Petersen, Lennart Minthon, Michael J Chao, Vivianna M Van Deerlin, Virginia M-Y Lee, Leslie M Shaw, John Q Trojanowski, Elaine R Peskind, Gail Li, Lea K Davis, Julia M Sealock, Nancy J Cox, Alison M Goate, David A Bennett, Julie A Schneider, Angela L Jefferson, Carlos Cruchaga, Timothy J Hohman
Cerebrospinal fluid (CSF) levels of amyloid-β 42 (Aβ42) and tau have been evaluated as endophenotypes in Alzheimer's disease (AD) genetic studies. Although there are sex differences in AD risk, sex differences have not been evaluated in genetic studies of AD endophenotypes. We performed sex-stratified and sex interaction genetic analyses of CSF biomarkers to identify sex-specific associations. Data came from a previous genome-wide association study (GWAS) of CSF Aβ42 and tau (1527 males, 1509 females). We evaluated sex interactions at previous loci, performed sex-stratified GWAS to identify sex-specific associations, and evaluated sex interactions at sex-specific GWAS loci...
July 2, 2018: Acta Neuropathologica
Adam J Svahn, Emily K Don, Andrew P Badrock, Nicholas J Cole, Manuel B Graeber, Justin J Yerbury, Roger Chung, Marco Morsch
Transactivating DNA-binding protein-43 (TDP-43) deposits represent a typical finding in almost all ALS patients, more than half of FTLD patients and patients with several other neurodegenerative disorders. It appears that perturbation of nucleo-cytoplasmic transport is an important event in these conditions but the mechanistic role and the fate of TDP-43 during neuronal degeneration remain elusive. We have developed an experimental system for visualising the perturbed nucleocytoplasmic transport of neuronal TDP-43 at the single-cell level in vivo using zebrafish spinal cord...
June 25, 2018: Acta Neuropathologica
Shunsuke Koga, Naomi Kouri, Ronald L Walton, Mark T W Ebbert, Keith A Josephs, Irene Litvan, Neill Graff-Radford, J Eric Ahlskog, Ryan J Uitti, Jay A van Gerpen, Bradley F Boeve, Adam Parks, Owen A Ross, Dennis W Dickson
Corticobasal degeneration (CBD) is a clinically heterogeneous tauopathy, which has overlapping clinicopathologic and genetic characteristics with progressive supranuclear palsy (PSP). This study aimed to elucidate whether transactive response DNA-binding protein of 43 kDa (TDP-43) pathology contributes to clinicopathologic heterogeneity of CBD. Paraffin-embedded sections of the midbrain, pons, subthalamic nucleus, and basal forebrain from 187 autopsy-confirmed CBD cases were screened with immunohistochemistry for phospho-TDP-43...
June 20, 2018: Acta Neuropathologica
John L Robinson, Maria M Corrada, Gabor G Kovacs, Myrna Dominique, Carrie Caswell, Sharon X Xie, Virginia M-Y Lee, Claudia H Kawas, John Q Trojanowski
The diagnosis of Alzheimer's disease (AD) in the oldest-old is complicated by the increasing prevalence of age-related neurofibrillary tangles, plaques and non-AD pathologies such as cerebrovascular disease (CVD), hippocampal sclerosis (HS), aging-related tau astrogliopathy (ARTAG), as well as TDP-43 and Lewy pathology. The contribution of these non-AD pathologies to dementia and cognitive resilience is unclear. We assessed the level of AD neuropathologic change (ADNPC) and non-AD pathology in 185 participants enrolled in The 90+ Study with available cognitive assessments and brain tissue...
June 18, 2018: Acta Neuropathologica
Maria Nolano, Vincenzo Provitera, Annamaria Stancanelli, Anna Maria Saltalamacchia, Giuseppe Caporaso, Francesco Lullo, Ilaria Borreca, Giuseppe Piscosquito, Stefania Mozzillo, Marcello Esposito, Fiore Manganelli, Bernardo Lanzillo, Lucio Santoro
No abstract text is available yet for this article.
June 18, 2018: Acta Neuropathologica
Kristian W Pajtler, Ji Wen, Martin Sill, Tong Lin, Wilda Orisme, Bo Tang, Jens-Martin Hübner, Vijay Ramaswamy, Sujuan Jia, James D Dalton, Kelly Haupfear, Hazel A Rogers, Chandanamali Punchihewa, Ryan Lee, John Easton, Gang Wu, Timothy A Ritzmann, Rebecca Chapman, Lukas Chavez, Fredrick A Boop, Paul Klimo, Noah D Sabin, Robert Ogg, Stephen C Mack, Brian D Freibaum, Hong Joo Kim, Hendrik Witt, David T W Jones, Baohan Vo, Amar Gajjar, Stan Pounds, Arzu Onar-Thomas, Martine F Roussel, Jinghui Zhang, J Paul Taylor, Thomas E Merchant, Richard Grundy, Ruth G Tatevossian, Michael D Taylor, Stefan M Pfister, Andrey Korshunov, Marcel Kool, David W Ellison
Of nine ependymoma molecular groups detected by DNA methylation profiling, the posterior fossa type A (PFA) is most prevalent. We used DNA methylation profiling to look for further molecular heterogeneity among 675 PFA ependymomas. Two major subgroups, PFA-1 and PFA-2, and nine minor subtypes were discovered. Transcriptome profiling suggested a distinct histogenesis for PFA-1 and PFA-2, but their clinical parameters were similar. In contrast, PFA subtypes differed with respect to age at diagnosis, gender ratio, outcome, and frequencies of genetic alterations...
June 16, 2018: Acta Neuropathologica
Rui Ryan Yang, Abudumijiti Aibaidula, Wei-Wei Wang, Aden Ka-Yin Chan, Zhi-Feng Shi, Zhen-Yu Zhang, Danny Tat Ming Chan, Wai Sang Poon, Xian-Zhi Liu, Wen-Cai Li, Rui-Qi Zhang, Yan-Xi Li, Nellie Yuk-Fei Chung, Hong Chen, Jingsong Wu, Liangfu Zhou, Kay Ka-Wai Li, Ho-Keung Ng
Pediatric low-grade gliomas (PLGGs) consist of a number of entities with overlapping histological features. PLGGs have much better prognosis than the adult counterparts, but a significant proportion of PLGGs suffers from tumor progression and recurrence. It has been shown that pediatric and adult low-grade gliomas are molecularly distinct. Yet the clinical significance of some of newer biomarkers discovered by genomic studies has not been fully investigated. In this study, we evaluated in a large cohort of 289 PLGGs a list of biomarkers and examined their clinical relevance...
June 14, 2018: Acta Neuropathologica
Atossa Shaltouki, Chung-Han Hsieh, Min Joo Kim, Xinnan Wang
Alpha-synuclein is a component of Lewy bodies, the pathological hallmark of Parkinson's disease (PD), and is also mutated in familial PD. Here, by extensively analyzing PD patient brains and neurons, and fly models, we show that alpha-synuclein accumulation results in upregulation of Miro protein levels. Miro is a motor/adaptor on the outer mitochondrial membrane that mediates mitochondrial motility, and is removed from damaged mitochondria to facilitate mitochondrial clearance via mitophagy. PD patient neurons abnormally accumulate Miro on the mitochondrial surface leading to delayed mitophagy...
June 9, 2018: Acta Neuropathologica
Florian Krach, Ranjan Batra, Emily C Wheeler, Anthony Q Vu, Ruth Wang, Kasey Hutt, Stuart J Rabin, Michael W Baughn, Ryan T Libby, Sandra Diaz-Garcia, Jennifer Stauffer, Elaine Pirie, Shahram Saberi, Maria Rodriguez, Assael A Madrigal, Zacharias Kohl, Beate Winner, Gene W Yeo, John Ravits
Sporadic amyotrophic lateral sclerosis (sALS) is the most common form of ALS, however, the molecular mechanisms underlying cellular damage and motor neuron degeneration remain elusive. To identify molecular signatures of sALS we performed genome-wide expression profiling in laser capture microdissection-enriched surviving motor neurons (MNs) from lumbar spinal cords of sALS patients with rostral onset and caudal progression. After correcting for immunological background, we discover a highly specific gene expression signature for sALS that is associated with phosphorylated TDP-43 (pTDP-43) pathology...
June 7, 2018: Acta Neuropathologica
Christian Koelsche, Martin Mynarek, Daniel Schrimpf, Luca Bertero, Jonathan Serrano, Felix Sahm, David E Reuss, Yanghao Hou, Daniel Baumhoer, Christian Vokuhl, Uta Flucke, Iver Petersen, Wolfgang Brück, Stefan Rutkowski, Sandro Casavilca Zambrano, Juan Luis Garcia Leon, Rosdali Yesenia Diaz Coronado, Manfred Gessler, Oscar M Tirado, Jaume Mora, Javier Alonso, Xavier Garcia Del Muro, Manel Esteller, Dominik Sturm, Jonas Ecker, Till Milde, Stefan M Pfister, Andrey Korshunov, Matija Snuderl, Gunhild Mechtersheimer, Ulrich Schüller, David T W Jones, Andreas von Deimling
Patients with DICER1 predisposition syndrome have an increased risk to develop pleuropulmonary blastoma, cystic nephroma, embryonal rhabdomyosarcoma, and several other rare tumor entities. In this study, we identified 22 primary intracranial sarcomas, including 18 in pediatric patients, with a distinct methylation signature detected by array-based DNA-methylation profiling. In addition, two uterine rhabdomyosarcomas sharing identical features were identified. Gene panel sequencing of the 22 intracranial sarcomas revealed the almost unifying feature of DICER1 hotspot mutations (21/22; 95%) and a high frequency of co-occurring TP53 mutations (12/22; 55%)...
June 7, 2018: Acta Neuropathologica
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