Free Neuropathology https://www.uni-muenster.de/Ejournals/index.php/fnp <p><em>Free Neuropathology</em> is a non-commercial journal that is run by Neuropathologists and other Neuroscientists and publishes papers on Human and Experimental Neuropathology. It is free for authors, free for readers, free from publishers, free from excessive formalities, and it encourages exchange of free opinions.</p> <p><em>Free Neuropathology</em> is not just another open-access online journal. It is a new type of journal edited and published by scientists working in the field. We do not have any financial interests, and we strongly feel that the huge amount of money currently spent for increasing the profit of publishers should be better invested into science. We believe that the usual activities of publishers such as copyediting, layout, hosting of articles, maintenance of the website and promotion could and should be overtaken by scientists in order to restitute scientific freedom. There is no article processing fee and no paywall -- the journal is free for everyone ("Diamond Open Access"). We try to reduce technicalities to a minimum. This grassroots development is managed by enthusiastic neuroscientists and it may be the future of publishing.</p> en-US <p>Papers are published open access under the Creative Commons BY 4.0 license.&nbsp;This license lets others distribute, remix, adapt, and build upon your work, even commercially, as long as they credit you for the original creation. Data included in the article are made available under the CC0 1.0 Public Domain Dedication waiver, unless otherwise stated, meaning that all copyrights are waived.</p> werner.paulus@uni-muenster.de (Werner Paulus) info@freeneuropathology.org (Ralf Mersmann) Wed, 01 Jan 2020 00:00:00 +0100 OJS 3.1.1.1 http://blogs.law.harvard.edu/tech/rss 60 Free for authors, free for readers, free from publisher, free formatting and free opinion: This is Free Neuropathology https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2610 <p>Free for authors, free for readers, free from publisher, free formatting and free opinion: This is Free Neuropathology</p> Werner Paulus ##submission.copyrightStatement## http://creativecommons.org/licenses/by/4.0 https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2610 Wed, 01 Jan 2020 00:00:00 +0100 Neuronal Transcriptome from C9orf72 Repeat Expanded Human Tissue is Associated with Loss of C9orf72 Function https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2911 <p>A hexanucleotide G<sub>4</sub>C<sub>2</sub> repeat expansion in <em>C9orf72</em> is the most common genetic cause of familial and sporadic cases of amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD). The mutation is associated with a reduction of C9orf72 protein and accumulation of toxic RNA and dipeptide repeat aggregates. The accumulation of toxic RNA has been proposed to sequester RNA binding proteins thereby altering RNA processing, consistent with previous transcriptome studies that have shown that the <em>C9orf72</em> repeat expansion is linked to abundant splicing alterations and transcriptome changes. Here, we used a subcellular fractionation method and FACS to enrich for neuronal nuclei from <em>C9orf72</em> repeat expanded <em>post-mortem</em> human ALS/FTD brains, and to remove neuronal nuclei with TDP-43 pathology which are observed in nearly all symptomatic <em>C9orf72</em> repeat expanded cases. We show that the <em>C9orf72</em> expansion is associated with relatively mild gene expression changes. Dysregulated genes were enriched for vesicle transport pathways, which is consistent with the known functions of C9orf72 protein. Further analysis suggests that the <em>C9orf72</em> transcriptome is not driven by toxic RNA but is rather shaped by the depletion of pathologic TDP-43 nuclei and the loss of <em>C9orf72</em> expression. These findings argue against RNA binding protein sequestration in neurons as a major contributor to <em>C9orf72</em> mediated toxicity.</p> Elaine Y. Liu, Jenny Russ, Edward B. Lee ##submission.copyrightStatement## http://creativecommons.org/licenses/by/4.0 https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2911 Fri, 21 Aug 2020 12:16:51 +0200 Clustering of activated microglia occurs before the formation of dystrophic neurites in the evolution of Aβ plaques in Alzheimer’s disease. https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2845 <p>Alzheimer’s disease (AD) is a late-onset disease that has proved difficult to model. Microglia are implicated in AD, but reports vary on precisely when and how in the sequence of pathological changes they become involved. Here, post-mortem human tissue from two differentially affected regions of the AD brain and from non-demented individuals with a high load of AD-type pathology (high pathology controls) was used to model the disease time course in order to determine how microglial activation relates temporally to the deposition of hallmark amyloid-β (Aβ) and hyperphosphorylated microtubule associated protein tau pathology. Immunofluorescence against the pan-microglial marker, ionised calcium-binding adapter molecule 1 (IBA1), Aβ and tau, was performed in the primary motor cortex (PMC), a region relatively spared of AD pathological changes, and compared to the severely affected inferior temporal cortex (ITC) in the same cases. Unlike the ITC, the PMC in the AD cases was spared of any degenerative changes in cortical thickness and the density of Betz cells and total neurons. The clustering of activated microglia was greatest in the PMC of AD cases and high pathology controls compared to the ITC. This suggests microglial activation is most prominent in the early phases of AD pathophysiology. Nascent tau inclusions were found in neuritic plaques in the PMC but were more numerous in the ITC of the same case. This shows that tau positive neuritic plaques begin early in AD which is likely of pathogenic importance, however major tau deposition follows the accumulation of Aβ and clustering of activated microglia. Importantly, findings presented here demonstrate that different states of microglial activation, corresponding to regional accumulations of Aβ and tau, are present simultaneously in the same individual; an important factor for consideration if targeting these cells for therapeutic intervention.</p> Patrick Jarmo Paasila, Danielle S Davies, Greg T Sutherland, Claire Goldsbury ##submission.copyrightStatement## http://creativecommons.org/licenses/by/4.0 https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2845 Tue, 04 Aug 2020 00:00:00 +0200 Treatment of autoimmune encephalomyelitis with a histone deacetylase inhibitor: Analyzing the role of immune-response genes https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2819 <p>We have previously shown that treatment of female NOD mice with a potent nonselective histone deacetylase inhibitor attenuated experimental autoimmune encephalomyelitis, a model for progressive multiple sclerosis. Herein we show that immunization with the MOG<sub>35-55</sub> peptide induced prolonged upregulation of genes encoding interleukin 17A (IL-17A), aryl hydrocarbon receptor, and histone deacetylase 11 in the spinal cord whereas the subunits of IL-27, IL-27p28 and IL-27ebi3 were significantly increased in secondary lymphoid organs after a lag period. Interestingly, the nitric oxide synthase gene was prominently expressed in both of these anatomic compartments following immunization. Treatment with the histone modifier repressed the transcription of all of these genes induced by immunization. Moreover, the drug suppressed the steady-state levels of the migration inhibitory factor and CD274 genes in both the spinal cord and peripheral lymphoid tissues. At the same time, the CD39 gene was downregulated only in secondary lymphoid organs. Paradoxically, the epigenetic drug enhanced the expression of Declin-1 in the spinal cord, suggesting a protective role in neuronal disease. Immunization profoundly enhanced transcription of the chemokine CCL2 in the secondary lymphoid tissues without a corresponding increase in the translation of CCL2 protein. Histone hyperacetylation neither altered the transcription of CCL2 nor its cognate receptor CCR2 in the central nervous system and peripheral lymphoid tissues. Surprisingly, the drug did not exert modulatory influence on most other immune response-related genes previously implicated in encephalomyelitis. Nevertheless, our data uncover several potential molecular targets for the intervention of experimental autoimmune encephalomyelitis that have implications for the treatment of progressive multiple sclerosis.</p> Arathi Jayaraman, Karen Avgush, Rashad Kulam, Advait Soni, Areeb Khan, Mourad Kerdjoudj, Sundararajan Jayaraman ##submission.copyrightStatement## http://creativecommons.org/licenses/by/4.0 https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2819 Tue, 14 Jul 2020 16:21:37 +0200 Neuronal intermediate filament inclusion disease may be incorrectly classified as a subtype of FTLD-FUS https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2639 <p><strong>Background</strong>: The majority of cases of frontotemporal lobar degeneration (FTLD) are characterized by focal cortical atrophy with an underlying tau or TDP-43 proteinopathy. A subset of FTLD cases, however, lack tau and TDP-43 immunoreactivity, but have neuronal inclusions positive for ubiquitin, referred to as atypical FTLD (aFTLD-U). Studies have demonstrated that ubiquitin-positive inclusions in aFTLD-U are immunoreactive for fused in sarcoma (FUS). As such, the current nosology for this entity is FTLD-FUS, which is thought to include not only aFTLD-U but also neuronal intermediate filament inclusion disease (NIFID) and basophilic inclusion body disease.</p> <p><strong>Objective</strong>: To compare pathological features of cases of aFTLD-U and NIFID.</p> <p><strong>Methods</strong>: We reviewed the neuropathology of 15 patients (10 males and 5 females; average age at death 54 years (range 41-69 years)) with an antemortem clinical diagnosis of a frontotemporal dementia and pathological diagnosis of aFTLD-U (n=8) or NIFID (n=7). Sections were processed for immunohistochemistry and immunoelectron microscopy with FUS, TDP-43, and α-internexin (αINX) antibodies.</p> <p><strong>Results</strong>: Eight cases had pathologic features consistent with FTLD-FUS, with severe striatal atrophy (7/8 cases), as well as FUS-positive neuronal cytoplasmic and vermiform intranuclear inclusions, but no αINX immunoreactivity. Five cases had features consistent with NIFID, with neuronal inclusions positive for both FUS and αINX. Striatal atrophy was present in only two of the NIFID cases. Two cases had αINX-positive neuronal inclusions consistent with NIFID, but both lacked striatal atrophy and FUS immunoreactivity. Surprisingly, one of these two NIFID cases had lesions immunoreactive for TDP-43.</p> <p><strong>Discussion</strong>: While FUS pathology remains a prominent feature of aFTLD-U, there is pathologic heterogeneity, including rare cases of NIFID with TDP-43- rather than FUS-positive inclusions.</p> Kevin F Bieniek, Keith Anthony Josephs, Wen-lang Lin, Dennis W Dickson ##submission.copyrightStatement## http://creativecommons.org/licenses/by/4.0 https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2639 Wed, 11 Mar 2020 13:04:06 +0100 Deposits of disease-associated alpha-synuclein may be present in the dura mater in Lewy body disorders: implications for potential inadvertent transmission by surgery https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2616 <p>Deposition of alpha-synuclein in the brain is a hallmark of Lewy body disorders. Alpha-synuclein has been considered to show prion-like properties. Prion diseases can be transmitted by the transplantation of cadaveric dura mater causing iatrogenic Creutzfeldt-Jakob disease. Recent observations of amyloid-β deposition in dural grafts support the seeding properties of amyloid-β. Here we assessed the presence of alpha-synuclein in dura mater samples as a potential transmissible seed source. We immunostained 32 <em>postmortem</em> dura mater samples; 16 cases with Lewy-body disorder (LBD) showing different pathology stages and 16 non-LBD cases for phosphorylated (Ser129) and disease-associated (5G4) alpha-synuclein. Disease-associated alpha-synuclein aggregates were identified in intradural nerve fibres and associated with a vessel in a single LBD-Braak stage 4 case. We conclude that alpha-synuclein is detectable, although rarely, in dura mater samples in patients with LBD. The risk of potential transmissibility of dural alpha-synuclein deserves assessment by complementary experimental studies.</p> Ellen Gelpi, Naomi P. Visanji, Selma Hönigschnabl, Angelika Reiner, Peter Fischer, Anthony Lang, Herbert Budka, Gabor G. Kovacs ##submission.copyrightStatement## http://creativecommons.org/licenses/by/4.0 https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2616 Wed, 12 Feb 2020 09:52:19 +0100 Multiple system atrophy - a clinicopathological update https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2813 <p>Multiple system atrophy (MSA) is a fatal, adult-onset neurodegenerative disorder of uncertain etiology, clinically characterized by various combinations of Levo-dopa-unresponsive parkinsonism, and cerebellar, motor, and autonomic dysfunctions. MSA is an α-synucleinopathy with specific glioneuronal degeneration involving striatonigral, olivopontocerebellar, autonomic and peripheral nervous systems. The pathologic hallmark of this unique proteinopathy is the deposition of aberrant α-synuclein (αSyn) in both glia (mainly oligodendroglia) and neurons forming pathological inclusions that cause cell dysfunction and demise. The major variants are striatonigral degeneration (MSA with predominant parkinsonism / MSA-P) and olivopontocerebellar atrophy (MSA with prominent cerebellar ataxia / MSA-C). However, the clinical and pathological features of MSA are broader than previously considered. Studies in various mouse models and human patients have helped to better understand the molecular mechanisms that underlie the progression of the disease. The pathogenesis of MSA is characterized by propagation of disease-specific strains of αSyn from neurons to oligodendroglia and cell-to-cell spreading in a "prion-like" manner, oxidative stress, proteasomal and mitochondrial dysfunctions, myelin dysregulation, neuroinflammation, decreased neurotrophic factors, and energy failure. The combination of these mechanisms results in neurodegeneration with widespread demyelination and a multisystem involvement that is specific for MSA. Clinical diagnostic accuracy and differential diagnosis of MSA have improved by using combined biomarkers. Cognitive impairment, which has been a non-supporting feature of MSA, is not uncommon, while severe dementia is rare. Despite several pharmacological approaches in MSA models, no effective disease-modifying therapeutic strategies are currently available, although many clinical trials targeting disease modification, including immunotherapy and combined approaches, are under way. Multidisciplinary research to elucidate the genetic and molecular background of the noxious processes as the basis for development of an effective treatment of the hitherto incurable disorder are urgently needed.</p> Kurt A. Jellinger ##submission.copyrightStatement## http://creativecommons.org/licenses/by/4.0 https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2813 Fri, 03 Jul 2020 13:29:12 +0200 Dementia with Lewy bodies – a clinicopathological update https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2613 <p>Dementia is one of the major burdens of our aging society. According to certain predictions, the number of patients will double every 20 years. Although Alzheimer’s disease (AD), as the most frequent neurodegenerative dementia, has been extensively analysed, less is known about dementia with Lewy bodies (DLB). Neuropathological hallmarks of DLB are the deposition of intracellular Lewy bodies (LB) and Lewy neurites (LN). DLB belongs to the α-synucleinopathies, as the major component of these inclusions is pathologically aggregated α-synuclein. Depending on the localization of LBs and LNs in the central nervous system cognitive and motor symptoms can occur. In our work, we will systematically review the possible etiology and epidemiology, pathological (both macroscopic and microscopic) features, structural and functional imaging findings, with a special emphasis on the clinico-pathological correlations. Finally, we summarize the latest clinical symptoms-based diagnostic criteria and the novel therapeutic approaches. Since DLB is frequently accompanied with AD pathology, highlighting possible differential diagnostic approaches is an integral part of our paper. Although our present knowledge is insufficient, the rapid development of diagnostic and research methods provide hope for better diagnosis and more efficient treatment, contributing to a better quality of life.</p> János Bencze, Woosung Seo, Abdul Hye, Dag Aarsland, Tibor Hortobágyi ##submission.copyrightStatement## http://creativecommons.org/licenses/by/4.0 https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2613 Tue, 18 Feb 2020 11:16:50 +0100 Top ten discoveries of the year: Neurodevelopmental disorders https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2672 <p>Developmental brain disorders, a highly heterogeneous group of disorders with a prevalence of around 3% of worldwide population, represent a growing medical challenge. They are characterized by impaired neurodevelopmental processes leading to deficits in cognition, social interaction, behavior and motor functioning as a result of abnormal development of brain. This can include developmental brain dysfunction, which can manifest as neuropsychiatric problems or impaired motor function, learning, language or non-verbal communication. Several of these phenotypes can often co-exist in the same patient and characterize the same disorder. Here I discuss some contributions in 2019 that are shaking our basic understanding of the pathogenesis of neurodevelopmental disorders. Recent developments in sophisticated <em>in-utero</em> imaging diagnostic tools have raised the possibility of imaging the fetal human brain growth, providing insights into the developing anatomy and improving diagnostics but also allowing a better understanding of antenatal pathology. On the other hand, advances in our understanding of the pathogenetic mechanisms reveal a remarkably complex molecular neuropathology involving a myriad of genetic architectures and regulatory elements that will help establish more rigorous genotype-phenotype correlations.</p> Mara Dierssen ##submission.copyrightStatement## http://creativecommons.org/licenses/by/4.0 https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2672 Wed, 15 Apr 2020 17:00:59 +0200 Top ten discoveries of the year: Neurodegeneration https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2634 <p>As we embark on a new year of scientific inquiry in neurodegenerative disease research, it is helpful to take a look back and consider the contributions in the field with the potential to be the most impactful. The purpose of this review is to highlight recent advances in 2019 which have the potential to be transformative in the field of neurodegenerative neuropathology. Substantive scientific progress rarely occurs as a “eureka moment”, and when possible, we opted to highlight collaborative efforts and research trends. We also included groundbreaking methodologies and tools. The generous increases in federal funding in the United States and elsewhere have massively expanded the total number of active programs researching Alzheimer’s disease. This exacerbates an imbalance, and an effort was made to highlight innovations across disease categories, and not to permit dementia to crowd out movement disorders, motor neuron disease, ataxias, etc. Thus, our overall goal was to highlight some of the most important discoveries, tools or methods that we feel will most likely directly enhance our ability to understand and diagnose neurodegenerative brain diseases. Given space limitations and the targeted readership of this journal, we selected ten topics most relevant to neuropathologists and clinical neuroscientists: 1. A new neurodegenerative disease category, 2. A new approach to probing gene expression on the single cell level, 3. A new approach merging histology and gene expression profiling, 4. A new computational approach using deep machine learning and computer vision, 5. A neuropathological substrate for sleep disturbance in Alzheimer’s disease, 6. A candidate pathogenic agent for Alzheimer’s disease, 7. A comprehensive approach to morphometric analysis of cerebellar neurodegeneration, 8. The strongest evidence yet linking neurodegeneration to contact sports, 9. Mounting evidence for gut to central nervous system transmission in Parkinson’s disease, and 10. A spotlight on glia in Huntington’s disease.</p> John Fonda Crary ##submission.copyrightStatement## http://creativecommons.org/licenses/by/4.0 https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2634 Wed, 08 Apr 2020 16:41:51 +0200 Top ten discoveries of the year: Neurotrauma https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2662 <p>Neurotrauma represents a major public health problem and is one of the leading causes of death and disability worldwide. Despite its high prevalence, there are major gaps in our understanding of the underlying patho-physiology leading to the substantial morbidity and mortality associated with this problem. Here, ten studies published in 2019 are reviewed that addressed issues related to the acute and long-term effects of neurotrau-ma. These studies can be broken down into three separate categories, namely, the importance of neurotrau-ma-based damage to the cerebrovascular unit, white matter damage following neurotrauma, and research related to the long-term neurodegenerative consequences of repeated head trauma, especially chronic trau-matic encephalopathy. The advances highlighted here indicate that progress has been made. However, major gaps in knowledge remain which will require additional neuropathologic studies of clinical specimens, as well as the development and investigation of a wide range of relevant pre-clinical models. Further efforts in this field are clearly needed if there are to emerge better clinical outcomes for the numerous patients that suffer neuro-trauma each year as well as those currently suffering from its long-term effects.</p> Daniel P Perl ##submission.copyrightStatement## http://creativecommons.org/licenses/by/4.0 https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2662 Mon, 30 Mar 2020 15:08:29 +0200 Top ten discoveries of the year: Neurooncology https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2671 <p>This article briefly discusses 10 topics that were selected by the author as top 10 discoveries published in 2019 in the broader field of neuro-oncological pathology (so including neurosciences as well as clinical neuro-oncology but with implications for neuro-oncological pathology). Some topics concern new information on immunohistochemical and molecular markers that enable improved diagnosis of particular tumors of the central nervous system (CNS) and information on a refined classification of medulloblastomas. Subsequently, several papers are discussed that further elucidate some pathobiological aspects of especially medulloblastomas (histogenesis, molecular evolution) and diffuse gliomas (mechanisms involved in CNS infiltration, role of cancer stem(-like) cells, longitudinal molecular evolution). The remaining topics concern progress made in vaccination therapy for glioblastomas and in using cerebrospinal fluid for liquid biopsy diagnosis of gliomas. Clearly, substantial, and sometimes even amazing progress has been made in increasing our understanding in several areas of neuro-oncological pathology. At the same time, almost every finding raises new questions, and translation of new insights in improving the outcome for patients suffering from CNS tumors remains a huge challenge.</p> Pieter Wesseling ##submission.copyrightStatement## http://creativecommons.org/licenses/by/4.0 https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2671 Wed, 26 Feb 2020 11:27:59 +0100 Top ten discoveries of the year: Neurovascular disease https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2615 <p>The aim of this review is to highlight novel findings in 2019 in the area of neurovascular disease. Experimental studies have provided insight into disease development, molecular determinants of pathology, and putative novel therapeutic targets. Studies in genetic experimental models as well as monogenic forms of human cere-brovascular diseases identified pathogenic molecules that may also be relevant to sporadic cases. There have been advances in understanding the development of cerebral cavernous angiomas and arteriovenous malfor-mations, and putative curative treatments have been suggested from experimental models. Key pathogenic pathways involved in vessel calcification and stiffness have also been identified. At the cellular level, studies showed that proper function of endothelial and mural cells, particularly pericytes, is crucial to ensure full endo-thelial differentiation and blood-brain barrier integrity. Moreover, recent discoveries support the existence of a homeostatic crosstalk between vascular cells and other neural cells, including neurons. Cerebrovascular diseas-es are strongly associated with inflammation. Beyond pathogenic roles of specific components of the inflam-matory response, new discoveries showed interesting interactions between inflammatory molecules and regu-lators of vascular function. Clinical investigation on cerebrovascular diseases has progressed by combining ad-vanced imaging and genome-wide association studies. Finally, vascular cognitive impairment and dementia are receiving increasing attention. Recent findings suggest that high-salt intake may cause cerebrovascular dys-function and cognitive impairment independent of hypoperfusion and hypertension. These and other recent reports will surely inspire further research in the field of cerebrovascular disease that will hopefully contribute to improved prevention and treatment.</p> Anna Maria Planas ##submission.copyrightStatement## http://creativecommons.org/licenses/by/4.0 https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2615 Thu, 30 Jan 2020 12:54:30 +0100 Top ten discoveries of the year: Neuromuscular disease https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2627 <p>This review highlights ten important advances in the neuromuscular disease field that either were first reported in 2019, or have reached a broad consensus during that year. The overarching topics include (i) new / emerging diseases; (ii) advances in understanding of disease etiology and pathogenesis; (iii) diagnostic advances; and (iv) therapeutic advances. Within this broad framework, the individual disease entities that are discussed in more detail include myoglobinopathy, <em>POPDC3</em>-mutated limb-girdle muscular dystrophy, neuromuscular adverse events associated with the immune checkpoint inhibition therapy, neuroglial stem cell-derived inflammatory pseudotumor of the spinal cord and spinal cord roots, acute flaccid myelitis, congenital myopathies, idiopathic inflammatory myopathies (with particular emphasis on immune-mediated necrotizing myopathies and sporadic inclusion body myositis), spinal muscular atrophy, and Duchenne muscular dystrophy. In addition, the review highlights several diagnostic advances (such as diagnostic RNA sequencing and development of digital diagnostic tools) that will likely have a significant impact on the overall neuromuscular disease field going forward.</p> Marta Margeta ##submission.copyrightStatement## http://creativecommons.org/licenses/by/4.0 https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2627 Thu, 23 Jan 2020 12:13:32 +0100 Top ten discoveries of the year: Neuroinflammation https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2612 <p>Ten neuropathological studies, published in 2019, are discussed, which address important aspects of neuroimmunology and inflammatory brain disease. They include topics related to new mechanisms of inflammation and immune mediated neurodegeneration, which are relevant for multiple sclerosis (publications 1 to 4) and discuss the role of specific autoantibodies against myelin oligodendrocyte glycoprotein or aquaporin 4 in neuromyelitis optica spectrum disorders (publications 5 and 6). Other studies highlight the discovery of new virus induced diseases of the nervous system and their relevance for clinical neurology and diagnostic neuropathology (publications 7 and 8). Finally, very interesting studies are discussed dealing with microglia and immune mechanisms in neurodegeneration (publication 9) and the neuropathological long-term outcome of Aß vaccination in Alzheimer’s disease (publication 10). All these studies highlight the central role of neuropathology in neurological disease research.</p> Hans Lassmann ##submission.copyrightStatement## http://creativecommons.org/licenses/by/4.0 https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2612 Fri, 10 Jan 2020 10:50:03 +0100 Optimizing filter trap assay for the detection of aggregated alpha-synuclein in brain samples https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2749 Thibauld Oullier, Alice Prigent, Guillaume Chapelet, Michel Neunlist, Franck Letournel, Pascal Derkinderen ##submission.copyrightStatement## http://creativecommons.org/licenses/by/4.0 https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2749 Tue, 28 Apr 2020 10:49:46 +0200 Enteric synucleinopathy: real entity or only a trendy concept? https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2920 <p class="AbstractText">An accumulating body of literature has emerged in the past 25 years to show that Parkinson’s disease (PD) is not only a disorder of the brain but also of the gastrointestinal tract and more generally of the gut-brain axis. Gastrointestinal symptoms occur in almost every PD patient at some point and in nearly every case examined pathologically autopsy studies find alpha-synuclein deposits, the pathological hallmarks of PD, in the enteric nervous system. This concept of ‘enteric synucleinopathy’ led to the hypothesis that the enteric nervous system might play a pivotal role in the initiation and spreading of PD. Although this hypothesis opens up interesting perspectives on the pathogenesis of neurodegenerative disorders, some important questions are still pending. The present opinion paper describes and compares the physiological and pathophysiological properties of alpha-synuclein in the brain and the enteric nervous system. We conclude that the existing data supports the existence of pathological alpha-synuclein species in the gut in PD. We also discuss if gut-brain interactions are important in other neurodegenerative disorders.</p> Adrien de Guilhem de Lataillade, Thibaud Lebouvier, Wendy Noble, Laurene Leclair-Visonneau, Pascal Derkinderen ##submission.copyrightStatement## http://creativecommons.org/licenses/by/4.0 https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2920 Fri, 28 Aug 2020 08:29:05 +0200 Studies on inflammation and stroke provide clues to pathomechanism of central nervous system involvement in COVID-19 https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2818 Adám Dénes, Dr, Stuart M Allan, Prof., Tibor Hortobágyi, Prof., Craig J Smith, Prof. ##submission.copyrightStatement## http://creativecommons.org/licenses/by/4.0 https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2818 Fri, 05 Jun 2020 11:48:09 +0200 Neuropathologists play a key role in establishing the extent of COVID-19 in human patients https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2736 <p>SARS-CoV2 infection causes COVID-19, &nbsp;and represents the most emergent health care crisis of our generation. Ample evidence in the scientific literature suggests that SARS-CoV, MERS-CoV, and endemic human coronaviruses infect brain cells.&nbsp; We delineate a rationale for encouraging evaluation of the brain, and in particular the brainstem, in COVID-19 so that potential neuropathological mechanisms can be delineated.</p> Lokman Cevik, Michele Joana Alves, Jose Javier Otero ##submission.copyrightStatement## http://creativecommons.org/licenses/by/4.0 https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2736 Thu, 02 Apr 2020 16:51:08 +0200 The “neuroepithelial tumor”: Exchanging our trash can for an industrial size dumpster? https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2611 <p>The “neuroepithelial tumor”: Exchanging our trash can for an industrial size dumpster?</p> Arie Perry ##submission.copyrightStatement## http://creativecommons.org/licenses/by/4.0 https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2611 Wed, 01 Jan 2020 00:00:00 +0100 Neuropathology through the ages https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2945 Kurt A. Jellinger ##submission.copyrightStatement## http://creativecommons.org/licenses/by/4.0 https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2945 Thu, 27 Aug 2020 10:25:29 +0200 The ’Accidental Neuropathologist' – on 40 Years in Neuropathology https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2956 Harry Vinters ##submission.copyrightStatement## http://creativecommons.org/licenses/by/4.0 https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2956 Tue, 25 Aug 2020 09:42:07 +0200 Between two worlds https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2933 Peter Lantos ##submission.copyrightStatement## http://creativecommons.org/licenses/by/4.0 https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2933 Mon, 17 Aug 2020 11:05:37 +0200 Neuropathology, my friend - on the paths of being and non-being https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2934 Ferenc Garzuly ##submission.copyrightStatement## http://creativecommons.org/licenses/by/4.0 https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2934 Tue, 11 Aug 2020 12:16:24 +0200 Reflections on an unconventional neuropathology career https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2903 Margaret Miriam Esiri ##submission.copyrightStatement## http://creativecommons.org/licenses/by/4.0 https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2903 Mon, 13 Jul 2020 11:44:49 +0200 Neuropathology through the ages – personal reflections https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2817 Herbert Budka ##submission.copyrightStatement## http://creativecommons.org/licenses/by/4.0 https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2817 Thu, 04 Jun 2020 15:34:11 +0200