Free neuropathology最新文献

{"title":"Neurotrauma: 2023 Update.","authors":"David S Priemer, Daniel P Perl","doi":"10.17879/freeneuropathology-2023-5076","DOIUrl":"10.17879/freeneuropathology-2023-5076","url":null,"abstract":"<p><p>2022 was a productive year for research in traumatic brain injury (TBI) and resultant neuropathology. After an extensive review, we present related studies and publications which we felt were of particular importance to the neuropathology community. First, 2022 was highlighted by important advancements in the diagnosis and, moreover, our understanding of chronic traumatic encephalopathy (CTE). Important publications include a pair concluding that CTE primarily concerns neuronal accumulation of phosphorylated tau (<i>ptau</i>), but that glial <i>ptau</i> accumulation often helps to facilitate diagnosis. In addition, a new large community study from Australia continues the indication that CTE is relatively uncommon in the community, and the first large-cohort study on brains of military personnel similarly demonstrates that CTE appears to be uncommon among service members and does not appear to explain high rates of neuropsychiatric sequelae suffered by the warfighter. The causation of CTE by impact-type TBI was supported by the application of the Bradford Hill criteria, within the brains of headbutting bovids, and interestingly within an artificial head model exposed to linear impact. Finally, a large-scale analysis of <i>APOE</i> genotypes contends that gene status may influence CTE pathology and outcomes. In experimental animal work, a study using mouse models provided important evidence that TDP-43 facilitates neurodegenerative pathology and is implicated in cognitive dysfunction following TBI, and another study using a swine model for concussion demonstrated that evidence that axonal sodium channel disruption may be a driver of neurologic dysfunction after concussion. Finally, we end with memoriam to Dr. John Q. Trojanowski, a giant of neurodegenerative research and an important contributor to the neurotrauma literature, who we lost in 2022.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"4 ","pages":"14"},"PeriodicalIF":0.0,"publicationDate":"2023-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10510742/pdf/freeneuropathol-04-14-5076.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41163307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurodegeneration: 2023 update.","authors":"John F Crary","doi":"10.17879/freeneuropathology-2023-4899","DOIUrl":"10.17879/freeneuropathology-2023-4899","url":null,"abstract":"<p><p>This paper reviews ten highly impactful studies published in the previous year selected by the author from the neurodegenerative neuropathology literature. As in previous years, the focus is to highlight human tissue-based experimentation most relevant to neuropathologists. A concerted effort was made to balance the selected studies across disease categories, approaches, and methodologies to capture the breadth of the research landscape. Studies include an integrated proteomic and transcriptomic study of Alzheimer disease (AD) and new consensus diagnostic neuropathological criteria for progressive supranuclear palsy. A number of studies looking at TAR DNA-binding protein 43 (TDP-43) are highlighted. One examined interaction between AD and limbic age-related TDP-43 encephalopathy (LATE) and yet another demonstrated how TDP-43 represses cryptic exon inclusion in <i>UNC13A</i>, suggesting a novel pathogenic mechanism. Most surprisingly, three cryogenic electron microscopy (cryo-EM) studies showed that <i>TMEM106B</i> filaments form the core of TDP-43-positive inclusions. Cryo-EM revealed a prion protein amyloid structure from aggregates in Gerstmann-Sträussler-Scheinker disease. There was an elegant functional genomic study cataloging microglial gene expression in the human brain. A study shed light on how <i>APOE</i> influences chronic traumatic encephalopathy. A pathoanatomical study tested the dual hit hypothesis of Lewy body progression throughout the nervous system. And finally, deep learning continues to show its promise with application of a weakly supervised multiple instance learning paradigm to assess aging post-mortem brains.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"4 ","pages":"13"},"PeriodicalIF":0.0,"publicationDate":"2023-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10484115/pdf/freeneuropathol-04-13-4899.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10225723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From amaurotic idiocy to biochemically defined lipid storage diseases: the first identification of GM1-Gangliosidosis.","authors":"Burkhard S Kasper, Christian Thomas, Anne Albers, Ekkehard M Kasper, Konrad Sandhoff","doi":"10.17879/freeneuropathology-2023-4845","DOIUrl":"10.17879/freeneuropathology-2023-4845","url":null,"abstract":"<p><p>On February 23^rd 1936, a boy-child (\"Kn\") died in an asylum near Munich after years of severe congenital disease, which had profoundly impaired his development leading to inability to walk, talk and see as well as to severe epilepsy. While a diagnosis of \"Little's disease\" was made during life, his postmortem brain investigation at Munich neuropathology (\"Deutsche Forschungsanstalt für Psychiatrie\") revealed the diagnosis of \"amaurotic idiocy\" (AI). AI, as exemplified by Tay-Sachs-Disease (TSD), back then was not yet understood as a specific inborn error of metabolism encompassing several disease entities. Many neuropathological studies were performed on AI, but the underlying processes could only be revealed by new scientific techniques such as biochemical analysis of nervous tissue, deciphering AI as nervous system lipid storage diseases, e.g. GM2-gangliosidosis. In 1963, Sandhoff & Jatzkewitz published an article on a \"biochemically special form of AI\" reporting striking differences when comparing their biochemical observations of hallmark features of TSD to tissue composition in a single case: the boy Kn. This was the first description of \"GM1-Gangliosidosis\", later understood as resulting from genetically determined deficiency in beta-galactosidase. Here we present illustrative materials from this historic patient, including selected diagnostic slides from the case \"Kn\" in virtual microscopy, original records and other illustrative material available. Finally, we present results from genetic analysis performed on archived tissue proving beta-galactosidase-gene mutation, verifying the 1963 interpretation as correct. This synopsis shall give a first-hand impression of this milestone finding in neuropathology. <b>Original paper:</b> On a biochemically special form of infantile amaurotic idiocy. Jatzkewitz H., Sandhoff K., Biochim. Biophys. Acta 1963; 70; 354-356. See supplement 1.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"4 ","pages":"12"},"PeriodicalIF":0.0,"publicationDate":"2023-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10413987/pdf/freeneuropathol-04-12-4845.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10372388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"6th Annual Conference of the Neuropathology Society of India (NPSICON) - Meeting Abstracts: February 23-25, 2023.","authors":"","doi":"10.17879/freeneuropathology-2023-4898","DOIUrl":"10.17879/freeneuropathology-2023-4898","url":null,"abstract":"<p><p><b>The 6^th Annual conference of the Neuropathology Society of India,</b> (NPSICON 2023) was held in a virtual mode, from 23^rd to 25^th February 2023, hosted by the Division of Neuropathology, Department of Pathology, Christian Medical College Vellore. Dr Geeta Chacko was the organizing Chairperson. The pre-conference workshop was on Fluorescence in situ hybridization with nearly 90 registrants. The workshop was conducted by NIMHANS Bangalore with Dr Shilpa Rao, Dr Vaishali Suri, Dr Vani Santosh and Dr Geeta Chacko as resource persons. There were 253 National registrants and 7 International registrations. The conference had participation from reputed national (34) and international (8) faculty and covered a wide range of topics in both neoplastic and non-neoplastic Neuropathology including sessions on perinatal pathology, epilepsy, neuromuscular pathology and several sessions in Neurooncology. There were five symposiums with several sessions of cases-based discussion. The first Prof Ashru K Banerjee oration was delivered by Dr Kenneth Aldape, from NIH Bethesda on: \"Practical Aspects of Methylation-Based Diagnostics in Central Nervous System Tumors\". The first Prof SK Shankar oration was delivered by Dr Avindra Nath, NIH Bethesda on \"Neuropathology of two pandemics: AIDS and COVID\". The Presidential oration was delivered by Dr Chitra Sarkar. The key note speakers included Dr Monika Hofer, Dr David Capper, Dr Takashi Komori and Dr Maysa Husseini. There were 28 papers for oral presentation and 38 posters. A highlight of the conference was a lively Quiz competition, which was held as the penultimate session. Despite being a virtual conference, there was active participation from all the delegates and the conference was very well received.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"4 ","pages":"9"},"PeriodicalIF":0.0,"publicationDate":"2023-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10280271/pdf/freeneuropathol-04-09-4898.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10032668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Postmortem changes in brain cell structure: a review.","authors":"Margaret M Krassner, Justin Kauffman, Allison Sowa, Katarzyna Cialowicz, Samantha Walsh, Kurt Farrell, John F Crary, Andrew T McKenzie","doi":"10.17879/freeneuropathology-2023-4790","DOIUrl":"10.17879/freeneuropathology-2023-4790","url":null,"abstract":"<p><p>Brain cell structure is a key determinant of neural function that is frequently altered in neurobiological disorders. Following the global loss of blood flow to the brain that initiates the postmortem interval (PMI), cells rapidly become depleted of energy and begin to decompose. To ensure that our methods for studying the brain using autopsy tissue are robust and reproducible, there is a critical need to delineate the expected changes in brain cell morphometry during the PMI. We searched multiple databases to identify studies measuring the effects of PMI on the morphometry (i.e. external dimensions) of brain cells. We screened 2119 abstracts, 361 full texts, and included 172 studies. Mechanistically, fluid shifts causing cell volume alterations and vacuolization are an early event in the PMI, while the loss of the ability to visualize cell membranes altogether is a later event. Decomposition rates are highly heterogenous and depend on the methods for visualization, the structural feature of interest, and modifying variables such as the storage temperature or the species. Geometrically, deformations of cell membranes are common early events that initiate within minutes. On the other hand, topological relationships between cellular features appear to remain intact for more extended periods. Taken together, there is an uncertain period of time, usually ranging from several hours to several days, over which cell membrane structure is progressively lost. This review may be helpful for investigators studying human postmortem brain tissue, wherein the PMI is an unavoidable aspect of the research.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"4 ","pages":"10"},"PeriodicalIF":0.0,"publicationDate":"2023-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10294569/pdf/freeneuropathol-04-10-4790.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9736416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurodevelopmental disorders: 2023 update.","authors":"Paulina Carriba, Nicola Lorenzón, Mara Dierssen","doi":"10.17879/freeneuropathology-2023-4701","DOIUrl":"10.17879/freeneuropathology-2023-4701","url":null,"abstract":"<p><p>Several advances in the field of neurodevelopmental diseases (NDDs) have been reported by 2022. Of course, NDDs comprise a diverse group of disorders, most of which with different aetiologies. However, owing to the development and consolidation of technological approaches, such as proteomics and RNA-sequencing, and to the improvement of brain organoids along with the introduction of artificial intelligence (AI) for biodata analysis, in 2022 new aetiological mechanisms for some NDDs have been proposed. Here, we present hints of some of these findings. For instance, centrioles regulate neuronal migration and could be behind the aetiology of periventricular heterotopia; also, the accumulation of misfolded proteins could explain the neurological effects in COVID-19 patients; and, autism spectrum disorders (ASD) could be the expression of altered cortical arealization. We also cover other interesting aspects as the description of a new NDD characterized by deregulation of genes involved in stress granule (SG) assemblies, or the description of a newly discovered neural progenitor that explains the different phenotypes of tumours and cortical tubers in tuberous sclerosis complex (TSC) disease; and how it is possible to decipher the aetiology of sudden unexplained death in childhood (SUDC) or improve the diagnosis of cortical malformations using formalin-fixed paraffin-embedded samples.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"4 ","pages":"8"},"PeriodicalIF":0.0,"publicationDate":"2023-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10280276/pdf/freeneuropathol-04-08-4701.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9711265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Memoirs of a neuropathologist who was unfit to be a clinician.","authors":"Hitoshi Takahashi","doi":"10.17879/freeneuropathology-2023-4741","DOIUrl":"10.17879/freeneuropathology-2023-4741","url":null,"abstract":"","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"4 ","pages":"7"},"PeriodicalIF":0.0,"publicationDate":"2023-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10280270/pdf/freeneuropathol-04-07-4741.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9711261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Survey of Neuroanatomic Sampling and Staining Procedures in Alzheimer Disease Research Center Brain Banks.","authors":"Juan C Vizcarra, Andrew F Teich, Brittany N Dugger, David A Gutman","doi":"10.17879/freeneuropathology-2023-4696","DOIUrl":"10.17879/freeneuropathology-2023-4696","url":null,"abstract":"<p><p>The collection of post-mortem brain tissue has been a core function of the Alzheimer Disease Research Center's (ADRCs) network located within the United States since its inception. Individual brain banks and centers follow detailed protocols to record, store, and manage complex datasets that include clinical data, demographics, and when post-mortem tissue is available, a detailed neuropathological assessment. Since each institution often has specific research foci, there can be variability in tissue collection and processing workflows. While published guidelines exist for select diseases, such as those put forth by the National Institute on Aging and Alzheimer Association (NIA-AA), it is of importance to denote the current practices across institutions. To this end a survey was developed and sent to United States based brain bank leaders, collecting data on brain region sampling, including anatomic landmarks used, staining (including antibodies used), as well as whole-slide-image scanning hardware. We distributed this survey to 40 brain banks and obtained a response rate of 95% (38 / 40). Most brain banks followed guidelines defined by the NIA-AA, having H&E staining in all recommended regions and targeted region-based amyloid beta, tau, and alpha-synuclein immunohistochemical staining. However, sampling consistency varied related to key anatomic landmarks/locations in select regions, such as the striatum, periventricular white matter, and parietal cortex. This study highlights the diversity and similarities amongst brain banks and discusses considerations when amalgamating data/samples across multiple centers. This survey aids in establishing benchmarks to enhance dialogues on divergent workflows in a feasible way.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"4 ","pages":"6"},"PeriodicalIF":0.0,"publicationDate":"2023-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10280272/pdf/freeneuropathol-04-06-4696.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9711266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"64th Meeting of the French Society of Neuropathology - Meeting Abstracts, December 2^nd, 2022.","authors":"","doi":"10.17879/freeneuropathology-2023-4776","DOIUrl":"10.17879/freeneuropathology-2023-4776","url":null,"abstract":"","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"4 ","pages":"5"},"PeriodicalIF":0.0,"publicationDate":"2023-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10280273/pdf/freeneuropathol-04-05-4776.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10032669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurooncology: 2023 update.","authors":"Michel Mittelbronn","doi":"10.17879/freeneuropathology-2023-4692","DOIUrl":"10.17879/freeneuropathology-2023-4692","url":null,"abstract":"<p><p>This article presents some of the author's neuropathological highlights in the field on neuro-oncology research encountered in 2022. Major advances were made in the development of more precise, faster, easier, less invasive and unbiased diagnostic tools ranging from immunohistochemical prediction of 1p/19q loss in diffuse glioma, methylation analyses in CSF samples, molecular profiling for CNS lymphoma, proteomic analyses of recurrent glioblastoma, integrated molecular diagnostics for better stratification in meningioma, intraoperative profiling making use of Raman effect or methylation analysis, to finally, the assessment of histological slides by means of machine learning for the prediction of molecular tumor features. In addition, as the discovery of a new tumor entity may also be a highlight for the neuropathology community, the newly described high-grade glioma with pleomorphic and pseudopapillary features (HPAP) has been selected for this article. Regarding new innovative treatment approaches, a drug screening platform for brain metastasis is presented. Although diagnostic speed and precision is steadily increasing, clinical prognosis for patients with malignant tumors affecting the nervous system remains largely unchanged over the last decade, therefore future neuro-oncological research focus should be put on how the amazing developments presented in this article can be more sustainably applied to positively impact patient prognosis.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"4 ","pages":"4"},"PeriodicalIF":0.0,"publicationDate":"2023-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10227754/pdf/freeneuropathol-04-04-4692.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10301648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}